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09-11-2007, 07:55
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The Science Of Dopamine
Ok. ~lostgurl~ and I decided to tie together all the material we could regarding dopamine, because we all know with out those nifty little things we wouldn't have much fun at all. In addition, this stuff just fascinates me and hopefully we can learn to understand it together. Obviously this isn't done yet, it's quite a project. Contribute! And let's hope I got the formatting correct! I didn't the first time! Again?! By the way...I'd like to develop some sort of receptor library? Possible? ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ DOPAMINERGIC SYSTEMS: DOPAMINE, THE DRUGS WHICH AFFECT IT, AND THE CONDITIONS RELATED TO IT ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ TABLE OF CONTENTS ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ I. THE NEUROCHEMISTRY OF DOPAMINE
B) BIOCHEMISTRY OF DOPAMINE C) BIOSYNTHESIS OF DOPAMINE D) BASICS OF SYNAPTIC TRANSMISSION E) SPECIFICS OF DOPAMINERGIC SYNAPSES F) DOPAMINERGIC AREAS OF THE BRAIN G) DOPAMINERGIC PATHWAYSII. PHARMACEUTICALS AND THE DOPAMINERGIC SYSTEM
B) INTRO TO DOPAMINERGIC PHARMACOLOGY C) OVER THE COUNTER MEDS, ETC, ETC. D) DRI'S E) DOPAMINE AGONISTS F) DOPAMINE ANTAGONISTS G) EUGEROIC DRUGS H) OTHER I) OTHER VARIOUS PHENETHYLAMINES J) PASSIVELY-DOPAMINERGIC CHEMICALS *) WARNINGS!!!III. MEDICAL CONDITIONS RELATED TO DOPAMINE UNDERSTIMULATION
B) SYMPTOMS C) RELATED DISORDERSIV. MEDICAL CONDITIONS RELATED TO DOPAMINE OVERSTIMULATION
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ PLAN FOR GUIDE: PART I DIAGRAMS FOR I-D MORE PURPOSES OF PKA'S IN I-E POSSIBLE MORE DETAILS ABOUT RECEPTORS IN I-E MUCH MORE DETAIL FOR I-F MORE INFO ABOUT PATHWAYS FOR I-G PART II SECTION A IS FINE SECTION B NEEDS INFO SECTION C IS FINE SECTIONS D-H NEED TO BE EXPANDED TO RESEMBLE SECTION G PART III/IV FOR SECTIONS PARTS 3&4 BREAK DOWN INTO INDIVIDUAL DISORDERS, DETAILS GALORE, SPECIFICS OF POSSIBLE RECEPTORS INVOLVED, ETC. PART V - REFERENCES TO BE DEVELOPED ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ I. THE NEUROCHEMISTRY OF DOPAMINE ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ A) What is Dopamine? Dopamine, also known as DA, is a neurotransmitter which is present in many animals. It can be defined as a phenethylamine, a natural compound synthesized from phenylalanine, or more specifically as catecholamine, a chemical compound which is synthesized from the amino acid tyrosine. As a catecholamine, dopamine is the biosynthetic precursor to norepinephrine and epinephrine, other notable and abundant neurotransmitters. Dopamine's structure as a phenethylamine and catecholamine also becomes important when we consider the vast number of other phenethylamines which can substitute dopamine due to homologous structures. Examples of these so-called substituted phenethylamines include 2C's, MDMA, dextroamphetamine, bupropion, and many many others. It should also be noted that in addition to dopamine's neurotransmission use, dopamine is also a neurohormone which stimulates the pituitary's release of another hormone, prolactin. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ B) Biochemistry of Dopamine: Standard Name: Dopamine Chemical Formula: C6H3(OH)2-CH2-CH2-NH2 Chemical Name: 4-(2-aminoethyl)benzene-1,2-diol Abbreviation: DA ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ C) How is Dopamine Biosynthesized? For the sake of simplicity explicit detail will not be given here. Essentially the base of dopamine is the amino acid tyrosine. Tyrosine, which is naturally biosynthesized in the body from phenylalanine, can also be acquired by means of supplements. Daily dosage suggestion is usually in the range of 500-1500mg though exceeding 12000mg/day can actually have negative effects and reduced dopamine levels significantly. Various sources identify the site of dopamine biosynthesis as either the ventral tegmental area or the substantia nigra pars compacta, though it is positive that dopamine is highly present in both.  Regardless of synthesis location, tyrosine is converted by means of the enzyme tyrosine hydroxylase into L-dihydroxyphenylalanine (also known as L-DOPA). DOPA is then converted to dopamine by means of a chemical reaction called decarboxylation using an enzyme known as dopa decarboxylase (this name is actually a misnomer of sorts for a lyase enzyme called aromatic L-amino acid decarboxylase which actually is used in 5-HTP to serotonin and tryptophan to tryptamine reactions as well. In some of the neurons this dopamine is then stored in vesicles for use, however, in others the dopamine is synthesized further to norepinephrine. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ NOW ONTO THE IMPORTANT STUFF! ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ D) Basics of Synaptic Transmission A synapse is specialized junction where a slim projection of the presynaptic neuron, known as the axon, arrives at branched projections of the post-synaptic cell, known as dendrites. The gap between the axon and the dendrites is estimated to be about 20nm and it is known as the synaptic cleft. When a nerve impulse, known as the action potential, comes through the pre-synaptic neuron it needs to reach the post-synaptic neuron, however, the action potential cannot cross the synaptic cleft. However, neurotransmitters are available to carry this action potential across the synaptic cleft (the process is sickeningly more difficult than this but such a basic understanding is all that is necessary) to the post-synaptic neuron where a receptor specializing in the traveling neurotransmitter with accept it and the impulse into the post-synaptic neuron. Obviously the transferring of this action potential causes a change in voltage of the post-synaptic neuron. This change is simply known as a post-synaptic potential. Synapses have one final feature which is rather important when discussing dopaminergic systems. When a neurotransmitter is released into the synapse, there are special proteins, known as neurotransmitter transporters, which exit one of the two synaptic membranes after the receptor reaction to pull it away from the synapse in order to recycle the neurotransmitter. This process is known as reuptake and plays the key role of ensuring receptors do not become desensitized. Receptors are also protected from desensitization by monoamine oxidases (MAOs) and catechol-O-methyl transferase (COMT), both of which are enzymes which serve to inactivate and break down specific neurotransmitters. The primary result of desensitization of receptors is a diminishing of the strength of the synapse. Note that it is also possible for neurotransmitter transporters to "reverse" their job in specific conditions, pulling neurotransmitters into the synapse. Synapses in the brain often have an added bit of difficulty because a neuron will often be forming synapses with several other neurons, not just another one. Though, these denser synapses do not operate any different (except in one case which is not of great importance here). ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ E) Specifics of Dopaminergic Synapses -Five types of dopamine receptors are known:
-Conversion of ATP to cAMP (as well as the left-over pyrophosphate) is catalyzed by adenylyl cyclase -Examples of biochemical purposes of protein kinases:
**Note that PKA's full name is cyclic adenosine monophosphate-dependent protein kinase meaning the enzyme's activity is dependent on which PKA and how much cAMP is present* ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ F) Dopaminergic Areas of the Brain Dopaminergic neurons are primarily concentrated in the ventral tegmental area and the substantia nigra pars compacta. However, this does not mean these are the only parts of the brain involved in dopaminergic processes. All known involved areas will now be briefly detailed: 1) ventral tegmental area -- (VTA) -- involved in reward circuit, incentive/motivation, pleasure, addiction 2) substantia nigra -- unpredictable rewards, learning, addiction mimics reward/learn pattern 3) frontal lobes -- pleasure, long-term memory, planning, drive/motivation 4) nucleus accumbens -- reward, laughter, pleasure, addiction, and fear 5) striatum -- planning, modulation of movement, executive function, reward feeling, motivation 6) arcuate nucleus -- neuroendocrine neurons 7) median eminence -- none; however, no blood brain barrier ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ G) Dopaminergic Pathways 1) mesocortical pathway -- One of the four major dopamine pathways in the human brain, the mesocortical pathway connects the ventral tegmentum with the frontal lobes of the cortex. In addition to its own purposes to run motivation and emotional response systems, the mescortical pathway is necessary to the proper function of the dorsolateral prefrontal cortex, which is the area most responsible for motor planning, organization, and regulation. Neg.) Flaws in this pathway are often the cause of the negative aspects of schizophrenia, including avolition (extreme lack of motivation), speech poverty, and flat affect 2) mesolimbic pathway -- Another of the four dopamine pathways in the brain. This major pathway links the ventral tegmentum with the nucleus accumbens, which is part of the striatum. The mesolimbic pathway is supposed to be essential in producing feelings of pleasure, as well as other feelings associated with reward and desire. Even though this pathway is highly connected with drug addiction, research shows it is not the euphoria that causes this here but rather incentive salience. Neg.) The excess of dopamine associated with psychosis and schizophrenia is linked solely to this region. Since researchers know this quite well, anti-psychotics can be developed to specifically target the dopamine receptors in this specific path. The mesolimbic is also well known for losing many dopamine neurons in the progression of Parkinson's though the lost neurons are relatively asymptomatic and thus is not an issue until a large percentage of neurons have been lost. 3) nigrostriatal pathway -- This is the third of the four dopamine pathways which happens to connect the substantia nigra with the striatum. Its key application is movement. Neg.) This location is of most worry when it comes to Parkinson's victim's lose of neurons, primarily due to speed rather than effect (like the mesolimbic the neurons lost here are barely noticed). This area seems to be especially sensitive to antipsychotics which cause tardive dyskinesia due to the abundance of movement neurons here. Even some simple antipsychotics meant to reduce psychosis have be known to cause parkinsonian movement issues. 4) tuberoinfundibular pathway -- The fourth dopamine pathway and the least neurotransmitter-based of them all. It seems most of the dopamine here is neuroendocrinal. Neg.) It seems abnormal lactation, disrupted menstrual cycles, visual issues, sexual dysfunction, and headache are caused when antipsychotics block dopamine here as a side effect, causing prolactin levels to increase in the blood. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ II. PHARMACEUTICALS AND THE DOPAMINERGIC SYSTEM *** *** *** *** *** *** *** NOTE: AUTHOR IS SIMPLY TRYING TO COMPILE INFO ON DRUGS RELATED TO THE DOPAMINERGIC SYSTEM. THIS IS NOT ALL-INCLUSIVE AND AUTHOR IS NOT RESPONSIBLE FOR INFORMATION NOT INCLUDED. INFORMATION PROVIDED IN "OTHER" SECTIONS SHOULD BE READ WITH CAUTION IN MIND. BE SAFE. *** *** *** *** *** *** *** ALSO, INFORMATION CONTAINED WITHIN THIS SECTION WAS DERIVED FROM THE FDA'S PROFESSIONAL MONOGRAPHS FOUND AT: WWW.DRUGS.COM *** *** *** *** *** *** *** ANY INFORMATION PERTAINING TO ILLICIT USE WAS FOUND AT : WWW.EROWID.ORG UNLESS OTHERWISE NOTED *** *** *** *** *** *** *** A) Quick Vocab -- Ampakine -- new drug class of modified benzamide compounds designed to enhance attention span and alertness -- Dopamine Reuptake Inhibitors -- drugs which bond to dopamine transports and prevent them from removing the DA from the synapse -- Dopamine Agonists -- drugs which attach to dopamine receptors and simulate dopamine -- Dopamine Antagonists -- drugs which attach to dopamine receptors and prevent dopamine from entering -- GABA (gamma-amoniobutyric acid) -- the primary inhibitory neurotransmitter in the CNS as well as the retina -- Prodrug -- a drug which is administered inactive and becomes an active compound in vivo -- Racemate (racemic) -- a mixture which is made of two molecules of identical structure but different chirality; thus, racemic - having equal amounts of left- and right-handed enantiomers -- RC -- research chemical ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ B) Introduction to Dopaminergic Pharmacology INFO SET TO COME SOON ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ C) Over-The-Counter Medications, Grey Market Items, Etc. CONTENTS: 1) PHENYLALANINE 2) TYROSINE 3) THEANINE (AKA L-THEANINE) 4) YOHIMBE 5) MUCUNA PRURIENS (TROPICAL VINE) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1) Phenylalanine SYSTEMATIC NAME: 2-Amino-3-phenyl-propanoic acid ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2) Tyrosine SYSTEMATIC NAME: (S)-2-Amino-3-(4-hydroxyphenyl)-propanoic acid
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 3) Theanine SYSTEMATIC NAME: 2-Amino-4-(ethylcarbamoyl)butyric acid Theanine is an amino acid which is believed to be found only in tea plants. The known neurochemical effects of theanine on the body are an increase of alpha brain waves as well as stimulating the production of the neurotransmitter GABA. Interestingly, theanine is actually an analogue of glutamate, the most common excitatory neurotransmitter as well as the precursor for GABA (the two neurotransmitters actually have counterbalancing effects), but despite being analogous to glutamate, it does not have quite the same affinity for glutamate receptors, rather simply stimulating release and/or production of GABA. This is the most likely cause of the relaxation and stress-relieving qualities of theanine. Theanine has shown potential medical uses for ADD/ADHD, PMS, and stress-relief.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 4) Yohimbine SYSTEMATIC NAME: 17α-hydroxy-yohimban-16α-carboxylic acid methyl ester Yohimbine is the alkaloid which comes from the bark of the West-African evergreen Yohimbe. It is known to be an antagonist of the alpha2-adrenergic receptor causing an increase in epinephrine and norepinephrine. It also antagonizes 4 seperate serotonin receptors and use shows an increase of dopamine (some reports of up to 80%) as well as monoamine oxidase ihibiting properties. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 5) Mucuna pruriens -tropical vine found in Central and South America shown to contain L-Dopa, Serotonin, 5-HTP, Nicotine, N,N-DMT, Bufotenine, and 5-MeO-DMT; despite L-Dopa being an excellent source of dopamine booster: A) too many other alkaloids in the plant and B) L-Dopa, as a dopamine agonist, runs a high risk of desensitization; likely little practice medical usage. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ D) Dopamine Reuptake Inhibitors CONTENTS 1) AMINEPTINE 2) BENZATROPINE 3) BUPROPION 4) COCAINE 5) CFT 6) DEXMETHYLPHENIDATE 7) DEXTROMETHORPHAN 8) INDATRALINE 9) LOMETOPANE 10) MESOCARB 11) METHYLENEDIOXYPYROVALERONE 12) METHAMPHETAMINE 13) METHYLPHENIDATE 14) NOMISFENSINE 15) PHEN(-DI-)METRAZINE 16) PROCYCLIDINE HYDROCHLORIDE 17) RTI-121 18) TROPARIL 19) VANOXERINE ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1) Amineptine -- (atypical tricyclic antidepressant) SYSTEMATIC NAME: Due to demonstrating abuse potential while on market it was discontinued in 2005 and is currently off-patent.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2) Benzatropine mesylate -- (anticholinergic) SYSTEMATIC NAME: In addition to reducing the effects of acetylcholine, as all anticholingergics do, benzatropine also acts as a dopamine reuptake inhibitor, primarily targeted at all forms of parkinsonism as well as for extrapyramidal disorders/symptoms (such as akinesia and akathisia), however, it is not to be prescribed for tardive dyskinesia). Given these extrapyramidal disorders/symptoms are often the result of anti-psychotics used for treatment of schizophrenia, benzatropine is often prescribed alongside the anti-psychotic treatment.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 3) Bupropion (Amfebutamone) -- (atypical antidepressant/nicotine antagonist) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 4) Cocaine -- (stimulant/appetite suppressant) SYSTEMATIC NAME: Cocaine's primary mechanism of action in the body is inhibition of monoamine uptake, which was demonstrated in rats at the ratio of 2:3 of serotonin to dopamine and 2:5 for serotonin to norepinephrine. The drug acts like all other MAOI's, by binding to transporters and preventing their function. Like many other dopaminergic drugs of abuse, cocaine is theorized to be highly linked to the ventral tegmental area, nucleus accumbens, and the frontal lobes of the cortex, since these areas are extremely rich in dopamine and receptors, as well as ties to the brain's "reward system."
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 5) CFT -- (stimulant/RC) SYSTEMATIC NAME: CFT is also sometimes known as beta-CFT or (-)-2[beta]-Carbomethoxy-3[beta]-(4-fluorophenyl)tropane. For the sake on being concise, it will only be referred to as CFT here. CFT is a dopamine reuptake inhibitor which is structurally an analogue of cocaine. In tests on animals, it has been shown to be 3-10 times more powerful than cocaine as well as lasting seven times longer. CFT's most common forms are a naphthalenedisulfonate salts, hydrochloride salts, and a free base. Despite thirty years of research, little is known about the compound and it has not history of human abuse.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 6) Dexmethylphenidate -- (stimulant) SYSTEMATIC NAME: This is nothing more than the dextro-isomer-only version of methylphenidate (most commonly known as Ritalin). It is designed as a more practical form of methylphenidate since it is thought that levomethylphenidate cause many of metabolic and unwanted side effects. Further information that would apply here will be found at methylphenidate.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 7) Dextromethorphan (DXM) -- (antitussive) SYSTEMATIC NAME: [pharmacological information will be added soon]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 8) Indatraline -- (monoamine reuptake inhibitor) SYSTEMATIC NAME: Also known as Lu 19-005, Indatraline, as a nonselective monoamine inhibitor, acts to block reuptake of norepinephrine, dopamine, and serotonin. It has also shown effects very similar to those of cocaine, however, less potent and may have potential as a treatment for cocaine addiction. [SWIM believes this is still a research chemical and this is all he has so far; look for updates]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 9) Lometopane -- (stimulant) SYSTEMATIC NAME: Also known by the chemical name "(-)-2[beta]-Carbomethoxy-3[beta]-(4-iodophenyl)tropane," Lometopane is a stimulant that is primarily used in research. Its structure is pheyltropane based and thus it potentially a cocaine analogue under US law. It is considered to be extremely potent and thus has use in measuring dopamine neuron damage and loss in Parkinson's patients. [SWIM, it seems, must delve deeper if he wants info about this one; check back.]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 10) Mesocarb -- (stimulant/antidepressant/anticonvulsive) SYSTEMATIC NAME: Due to it being a Soviet-developed drug, Mesocarb is still widely unknown and unsearched by the West. Acting as dopamine reuptake inhibitor it is said to be slower acting, longer lasting, and less neurotoxic than dextroamphetamine. [Beyond this SWIM doesn't want to detail much more because the only English-language source of info found was Wikipedia and due to the nature of the info and his inability to cross-reference with the Russian links he didn't want to put it on here yet; check back.]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 11) Methylenedioxypyrovalerone -- (stimulant/NERI) SYSTEMATIC NAME: Also known as MDPV or MDPK, this drug is a designer drug with no history of medical use. It inhibits reuptake of norepinephrine and dopamine, apparently with the potency of four times that of methylphenidate. Although it does not hold illegal status in any country, it may possibly be fall under analogue illegal status (bears a semblance to ecstacy and other MDxx's) in countries with analogue laws. [Information here will clearly be rough and possibly inaccurate; SWIM will post for now but check back later.]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 12) Methamphetamine -- (psychostimulant/sympathomimetic) SYSTEMATIC NAME: [Pharmacology will be up soon; SWIM wants to research a bit more and distinguish isomers.]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 13) Methylphenidate -- (stimulant) SYSTEMATIC NAME: Though often deemed a dopamine reuptake inhibitor, not enough is known about the drug pharmacologically to make that declaration. The leading theory on its mechanism is that it activates the brain stem's arousal system as well as the cortex. As far as monoamines go, there have been some affinities noted. Studies show methylphenidate does have a affinity for bind to dopamine and norepinephrine transporters. Furthermore, the more active dextro- isomer of methylphenidate has a quite notable affinity for norepinephrine specifically. Both isomers also displayed an affinity for 5HT receptors but no acts of binding were recorded. Also noteworthy is a 2004 study which showed that methylphenidate does act as a reuptake inhibitor for dopamine and, like amphetamines, they cause a release of dopamine. However, methylphenidate seemed to release old stores of dopamine while amphetamines seemed to be using newly produced dopamine. Regardless, we still have no conclusive answers.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 14) Nomifensine SYSTEMATIC NAME: Sometimes known as Merital, nomifensine was a fairly typical dopamine reuptake inhibitor researched and used primarily in the 1970's and 1980's for use as an antidepressant. The drug was also researched for use in ADHD and Parkinson's, however, despite successful animal testing, the drug seemed not to benefit human subjects. Despite being originally quite well recieved due to effectivness, few adverse effects, and little abuse potential, it is no longer used in medicine due to stimulant abuse potential, anemia, kidney and liver toxicity, overstimulation, and hyperthermia. Despite this, it is still used in research of links between dopamine and addiction due to one of its more unique effects on the brain.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 15) Phen(-di-)metrazine -- (stimulant/anorectic) SYSTEMATIC NAME: Closely tied to older pharmaceutical methods of weight loss, phendimetrazine is chemically related to amphetamine. Little is actually known about the drug's mechanism though it is known that about 30% of it metabolizes into phenmetrazine once administered. Phenmetrazine is an ancestor pharmaceutical of phendimetrazine. Phenmetrazine, known as Preludin, was quite popular in the 1950's because it had less side effects and yet was more effective than amphetamine as a weight loss solution. However, the fact that it had less side effects, and also because the manufacturers claims that is was less euphoric was probably not true (it was considered more euphoric by some), led to it having quite an appeal among amphetamine addicts. The drug was pulled off the market by the late-fifties, though this was likely due to reports of psychosis similar to that which is amphetamine-induced. Regardless, the actual pharmacology of phendimetrazine is not well known and in recent years it is rarely prescribed in any case.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 16) Procyclidine hydrochloride -- (anticholinergic) SYSTEMATIC NAME: This drug is commonly used for treatment of parkinsonism and drug-induced extrapyramidal symptoms. [As far as the pharmacology of the drug, not even the FDA clinical/professional fact sheet has much more than that. SWIM will hunt; check back later.]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 17) RTI-121 -- (highly selective DRI) SYSTEMATIC NAME: This phenyltropane (structurally similar to cocaine) based stimulant was developed in the 1990's and is reserved for research purposes. Its high potency and duration imply many risks for human abuse, however, due to its transporter binding process and speed it is theorized to have a lower abuse potential than cocaine. Due to its very specific binding with dopamine transporters it is most useful in mapping dopamine in research studies.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 18) Troparil -- (stimulant/RC) SYSTEMATIC NAME: This is yet another research chemical that acts as a dopamine reuptake inhibitor and is phenyltropane based. It has been shown to be equal in potency to cocaine although the duration is much longer, due to the absence of the link, which was easily and quickly metabolized, that connects the phenyl and tropane parts. It is used in research for dopamine mapping. Human abuse has not yet been documented, likely due to high cost (see note below about legality).
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ E) Dopamine Agonists CONTENTS 1) APOMORPHINE 2) BROMOCRIPTINE 3) DIHYDROERGOCRYPTINE 4) FENCAMFAMINE 5) LEVODOPA 6) LISURIDE 7) MESULERGINE 8) METERGOLINE 9) PERGOLIDE 10) PRAMIPEXOLE 11) ROPINIROLE 12) ROTIGOTINE ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1) Apomorphine -- (emetic) SYSTEMATIC NAME: This potent and non-ergoline dopamine agonist is primarily prescribed as a treatment for Parkinson's disease. The drug displays primary affinities for all dopamine receptors (from order of strongest to least: 4, 5, 3, 2, 1) as well as the 1D, 2B, and 2C adrenergic receptors. It is believed that the stimulation of the D2 receptors of the caudate-putamen is the drug's primary mechanism although that is just theoretical. The drug is also sometimes prescribed for erectile dysfunction.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2) Bromocriptine mesylate -- (ergoline-based) SYSTEMATIC NAME: Ergotaman-3',6',18-trione, 2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'alpha-(2-methylpropyl)- This dopamine agonist, derived from ergoline, is primarily used in the treatment of pituitary tumors and Parkinson's disease.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 3) Dihydroergocryptine -- (ergoline-based) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 4) Fencamfamine -- (stimulant/appetite suppressant) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 5) Levodopa -- (prodrug) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 6) Lisuride -- (iso-ergoline) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 7) Mesulergine -- (ergoline-based) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 8) Metergoline -- (ergoline-based) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 9) Pergolide -- (ergoline-based) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 10) Pramipexole -- (non-ergoline) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 11) Ropinirole -- (non-ergoline) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 12) Rotigotine -- (non-ergotamine) SYSTEMATIC NAME:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ F) Dopamine Antagonists CONTENTS 1) AMOXAPINE 2) ARIPIPRAZOLE 3) CLOZAPINE 4) DROPERIDOL 5) DOMPERIDONE 6) METOCLOPRAMIDE 7) OLANZAPINE 8) QUETIAPINE 9) RISPERIDONE 10) ZIPRASIDONE ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1) Amoxapine -- (tricyclic anti-depressant) SYSTEMATIC NAME: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2) Aripiprazole -- (aypical anti-psychotic) SYSTEMATIC NAME: 7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 3) Clozapine -- (atypical anti-psychotic) SYSTEMATIC NAME: 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepine ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 4) Droperidol SYSTEMATIC NAME: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 5) Domperidone SYSTEMATIC NAME: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 6) Metoclopramide SYSTEMATIC NAME: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 7) Olanzopine SYSTEMATIC NAME: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 8) Quetiapine SYSTEMATIC NAME: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 9) Risperidone SYSTEMATIC NAME: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 10) Ziprasidone SYSTEMATIC NAME: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ G) Eugeroics CONTENTS 1) ADRAFINIL 2) CX717 3) MODAFINIL ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1) Adrafinil -- (stimulant/prodrug) SYSTEMATIC NAME: Adrafinil is nothing more than the earlier and prodrug form of modafinil. Modafinil likely became preferred and thus manufactured due to quicker onset of effects.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2) CX717 -- (ampakine) SYSTEMATIC NAME: Researched drug which stimulates glutamate and presumably AMPA receptors and shows possible use for ADHD and Alzheimer's. The drug has some problems with the FDA. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 3) Modafinil -- (stimulant) SYSTEMATIC NAME: [SWIM needs to really sift through this FDA report to get things straight. If you need the info it can all be found here: http://www.drugs.com/pro/provigil.html ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ H) Other CONTENTS 1) AMPHETAMINE (AKA SPEED, ADDERALL, DEXEDRINE, DEXTROAMPHETAMINE) 2) CATHINONE (INCL. METHCATHINONE, KHAT; AKA CAT, METHCAT) 3) 4-METHYL-AMINOREX (INCL. ALL AMINOREX ANALOGUES?) 4) PEMOLINE 5) LYSERGIC ACID DIETHYLAMIDE 6) BENZYLPIPERAZINE ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1) Amphetamine -- (stimulant) SYSTEMATIC NAME: Amphetamine belongs in a seperate category from the other dopaminergics because it does not act like any of the either two main classes. Amphetamines only two mechanisms of action are a forced expulsion of dopamine contained in synaptic vesicles as well as amphetamines affinity for the DATs (dopamine active transporter), which takes control of it, denying it it's ability to clear the synapse of dopamine. Although this second act is technically reuptake inhibition, SWIM considers amphetamines to be certainly not dopamine reuptake inhibitors. [SWIM hopes that is the only time his personal opinion must be used.] Additional FDA material shows the drug to also act somewhat as an MAOI, preventing monoamine oxidases from breaking down dopamine to homovanillic acid, although methamphetamines, due to the additional methyl group, are much more effective as an MAOI.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2) Cathinone/Methcathinone -- (stimulant) SYSTEMATIC NAME: Cathinone is an alkaloid present in the leaves of the shrub, Khat, and methcathinone is one of its analogues, which is synthetic. Methcathinone does not cross the blood-brain barrier as well as methamphetamines due to a slightly polar bond in its structure, but in other ways acts quite similar. The drug acts as both a serotonin and dopamine reuptake inhibitor. It is not known to have any effects on the norepinephrinergic system. The lack of these effects is the likely reason for its placement as a Schedule I substance, since it likely has no uses in treatment of ADD/ADHD.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 3) 4-Methyl-aminorex SYSTEMATIC NAME: 4-methyl-5-phenyl-2-amino-oxazoline ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 4) Pemoline SYSTEMATIC NAME: 2-amino-5-phenyl-1,3-oxazol-4-one ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 5) Lysergic acid diethylamide (LSD) SYSTEMATIC NAME: (6aR,9R)-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3-fg]quinoline-9-carboxamide ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 6) Benzylpiperazine (BZP) SYSTEMATIC NAME: 1-benzylpiperazine ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ I) OTHER VARIOUS PHENETHYLAMINES CONTENTS NEED TO RESEARCH - - http://en.wikipedia.org/wiki/Categor...henethylamines ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ J) PASSIVELY-DOPAMINERGIC CHEMICALS CONTENTS 1) ALCOHOL 2) CAFFEINE 3) IBOGAINE 4) THC ***ALSO AT LEAST SOME OPIOIDS---RESEARCH ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1) Alcohol SYSTEMATIC NAME: Ethanol ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2) Caffeine SYSTEMATIC NAME: 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 3) Ibogaine SYSTEMATIC NAME: 12-Methoxyibogamine ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 4) THC (Δ9-tetrahydrocannabinol) SYSTEMATIC NAME:
(−)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ K) CHEMICALS WITH UNIQUE DOPAMINERGIC EFFECTS CONTENTS 1) GAMMA-BUTYROLACTONE 2) GAMMA-HYDROXYBUTYRIC ACID 3) NICOTINE ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 1) Gamma-Butyrolactone (GBL) SYSTEMATIC NAME: Dihydrofuran-2(3H)-one ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2) Gamma-Hydroxybutyric Acid (GHB) SYSTEMATIC NAME: 4-Hydroxybutanoic acid ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 3) Nicotine SYSTEMATIC NAME: (S)-3-(1-Methyl-2-pyrroli-dinyl)pyridine ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ POSSIBLE EFFECTS OF DRI/AGONIST USE: *TOLERANCE: AS NOTED BEFORE IN PART I, NEUROTRANSMITTER TRANSPORTERS SERVE THE PURPOSE OF REUPTAKE THE NEUROTRANSMITTER FOR RECYCLING IN ORDER TO PROTECT THE RECEPTOR FOR CONSTANT STIMULATION. USE OF ANY DOPAMINE REUPTAKE INHIBITOR OR DOPAMINE AGONIST (AMPHETAMINE INCLUDED) OVER A PERIOD OF TIME OR IN AN ABUSIVE FASHION CAN RESULT IN DESENSITIZATION OF THE RECEPTOR RESULTING IN TOLERANCE. YES, THIS IS TOLERANCE BUILD-UP IN DOPAMINERGICS. IF YOU ABUSE YOU NEUROCHEMICAL SYSTEM IT MAY CHANGE ON YOU.* *AMPHETAMINE PSYCHOSIS (STIMULANT PSYCHOSIS): WHEN USING STIMULANTS FOR EXTENDED PERIODS OF TIME (THIS RISK IS ESPECIALLY PRESENT WITH AMPHETAMINES AND METHAMPHETAMINES) IT IS POSSIBLE TO BECOME PSYCHOTIC. THOUGH THIS STATISICALLY ONLY OCCURS WITH CHRONIC USERS AND BINGE DOSES, IT IS POSSIBLE FOR IT TO HAPPEN OFF JUST ONE DOSE. WATCH WHEN COMBINING ANY DRUGS WHICH STIMULATE THE BODIES DOPAMINERGIC SYSTEM: THE CAUSE OF THIS IS LIKELY A FLOODING OF DOPAMINE INTO THE MESOLIMBIC PATHWAY (SLEEP DEPRIVATION ASSISTS THE PSYCHOSIS) AND SUBSEQUENTLY THE DOPAMINE CANNOT BE EXPELLED. THIS EXPERIENCE IS NEUROCHEMICALLY AND PHYSICALLY EQUIVALENT TO BEING TEMPORARILY SCHIZOPHRENIC. BE CAREFUL!* ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ III. MEDICAL CONDITIONS OF DOPAMINE UNDERSTIMULATION Causes of Dopamine Deficiency Although we understand very little about the causes or underlying reasons for the understimulation of dopamine receptors and the conditions which can derive from that, we know that, if dopamine understimulation is the case, then it must be a case of either excessively low dopamine levels in the brain or permanantly damaged or faulty receptors. At this point in history we understand very little about these conditions but know that they can result from the following: 1) Genetics - 2) Diet - 3) Drug Abuse - Just as often as the cause of a dopaminergic is discovered, one is given up on, without a diagnosis. Symptoms of Dopamine Deficiency -Fatigue -Inability to concentrate -Difficulty with decision making and problem solving -Cravings for meth, coffee, nicotine, or food -Loss of interest in sex or inability to climax -Lack of motivation, even for hobbies -Depression (characterized by inability to feel joy and pleasure) -Low energy levels -Lethargy -Tremor -Attention deficits -Trouble with memory -Social anxiety Disorders Believed To Be Caused By Insufficient Dopamine Stimulation -Restless Legs Syndrome (RLS) -Parkinson's Disease -ADD/ADHD -Depression ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ IV. MEDICAL CONDITIONS OF DOPAMINE OVERSTIMULATION Disorders Believed To Be Caused By Excess Dopamine Stimulation -Schizophrenia -Amphetmaine Psychosis -Tourette's Syndrome -Impulsive Behavior ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ V. SOURCES AND REFERENCES II-D-13: http://findarticles.com/p/articles/mi_qa3892/is_200404/ai_n9356900 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ VI. THINGS FOR FURTHER INVESTIGATION neurotransmitters http://www.benbest.com/science/anatmind/anatmd10.html serotonin syndrome http://www.uspharmacist.com/oldformat.asp?url=newlook/files/feat/acf2fa6.htm GABA https://www.neurorelief.com/newsletterarchive.php?issue=237 theanine http://www.delano.com/Articles/Theanine-Sharpe.html pharmacokinetics http://www.boomer.org/c/p4/#topics pKa http://www.chemicalforums.com/index.php?page=pkavalues receptor affinities! http://pdsp.med.unc.edu/pdsp.php Last edited by jazzmetalguitar; 12-11-2007 at 09:06.. Reason: add pics 
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#2
09-11-2007, 18:16
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Re: The Science Of Dopamine
Fascinating, and good job!
One suggestion: For short-sighted flamingos could it be in Verdana 2?
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#3
09-11-2007, 18:51
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Re: The Science Of Dopamine
Theanine is generally known to decrease serotonin, not increase it.
Theanine-induced reduction of brain serotonin concentration in rats. Yokogoshi H, Mochizuki M, Saitoh K. Laboratory of Nutritional Biochemistry, School of Food and Nutritional Sciences, University of Shizuoka, Japan. yokogosi@fnsl.u-shizuoka-ken.ac.jp Following the administration of theanine, the brain tryptophan content significantly increased or tended to increase, but the contents of serotonin and 5-hydroxyindole acetic acid (5HIAA) decreased. The use of inhibitors of serotonin metabolism enable us to speculate that theanine reduced serotonin synthesis and also increased serotonin degradation in the brain. PMID: 9614715 [PubMed - indexed for MEDLINE] |
