Some Basic Pharmacology; cannabinoids, uppers, downers, and opioids
This is a report I wrote just for fun, it's not really complete and anyone is welcome to add whatever they would like. It concerns some basic pharmacology and history reguarding cannabinoids, stimulants, depressants, and opioids. Hope someone finds something interesting in here.
The cannabinoids are a system of naturally-occurring chemicals found in the plant cannabis sativa. The most widely studied cannabinoid, delta-9-tetrahydrocannabinol, is found in higher concentrations than the other cannabinoids. Cannabinol (CBN) and cannabidol (CBD) act on CB2 receptors in the body, while delta-9-THC acts on CB1 receptors. These are subgroups of a naturally-occurring system to which the endogenous ligands, anandamide and 2-AG adhere. These endogenous ligands mimic the action of the cannabinoids.
The amphetamines are a group of drugs known to cause central-nervous-system stimulation and appetite reduction. Amphetamine was first synthesized in 1889 from ephedrine, an alkaloid of the plant ma huang. It was not used medically until the 1930’s, when it resurfaced as a treatment for asthma. Amphetamine abuse was noted by professionals and a crack-down on illicit amphetamine use was issued by the government in 1965. Today, amphetamine is still an active part of The United States pharmacopoeia as a treatment for attention deficit/hyperactivity disorder. The use of amphetamine as a weight-loss drug has long-been done away with. A new class of drugs, known as anorectics, was created to mimic the appetite-suppressant properties of amphetamine without the burden of its high abuse liability. Drugs in this class include phentermine (Fastin), diethylpropion (Tenuate), and phendimetrazine (Prelu-2). One drug in this class, known as phenmetrazine (Preludin), has been shown to have an abuse liability profile greater than that of methamphetamine; for this reason, it is rarely prescribed anymore.
Cocaine is an alkaloid of the coca plant. In the form of its hydrochloride salt, cocaine is a white solid which is known as crack. Cocaine is not water-soluble unless it’s in the form of a salt, and usually appears as a white to off-white, chalky powder which can form clumps when pressure is applied. Cocaine is a central-nervous-system stimulant. Cocaine is a dopamine re-uptake inhibitor and has the highest affinity for sites located in the striatum of the brain. Cocaine causes an increase in locomotive behavior and a decrease in appetite. It’s also a very effective topical anesthetic; in fact, several analogues of cocaine are used quite often in medical practice (benzocaine, lidocaine, novacaine.) These drugs never cross the blood-brain barrier.
Another drug that’s worth mentioning is known by the brand-name Ritalin (methylphenidate). Methylphenidate is a dopamine re-uptake inhibitor and competes with cocaine for the same binding sites in the striatum. Methylphenidate was synthesized in the mid-20th century as a treatment for AD/HD without the appetite suppression of other drugs used to treat this condition.
Caffeine is the most popular psychoactive in the world. It occurs naturally in the coffee bean, the tea leaf, the beetle nut, and the kola nut. Caffeine is an adenosine a-2 antagonist. Adenosine is a neurotransmitter that builds up when you are fatigued. By antagonizing the adenosine receptors, caffeine indirectly causes an increase in dopamine and norepinephrine in the mesolimbic tract of the brain. This is why caffeine is addictive. The reinforcing effects of caffeine have been proven, as baboons will readily self-administer doses of caffeine.
Pemoline is a central-nervous-system stimulant that acts like other sympathomimetics. Since 2005, it has been off the market due to the risk of adverse side-effects. An illegal pemoline analog, 4-methylaminorex, has gained some popularity as an alternative to methamphetamine.
Another interesting group of drugs used as stimulants are known as eugeroics, literally “good arousal” drugs. This group includes adrafinil and modafinil. They are used as antinarcoleptics and belong to a chemical group known as the ampakines. These drugs work by facilitating the excitatory neurotransmitter glutamate. This method of action is unique when compared to that of other stimulants.
The phenethylamines are partial analogs to the amphetamines. Phenethylamines include methylenedioxymethamphetamine (MDMA, extacy), methylenedioxyamphetamine (MDA, eve), 2C-T-2, 2C-T-2, DOB, 2C-B (nexus). These drugs act on 5-hydroxytriptamine subtype 2 receptors as well as dopamine subtype 2 receptors. They are half-and-half ligands to these receptors. They induce stimulation and euphoria as well as feelings of empathy and forgiveness, which make these drugs popular. They are most commonly found at all night dancing parties, more commonly called raves. People who ingest MDMA can dance all night without experiencing fatigue. Analogs that induce a “body high” include 2C-B, 2C-T-2 and 2C-7, as well as DOM and DOB. These drugs are more psychedelic than MDMA and MDA. They act primarily on 5-hydroxytriptamine subtype 2 receptors rather those dopamine subtype 2 receptors. They are also stimulating like the amphetamine and methamphetamine analogs but the stimulating activity is due to 5-hydroxytriptamine receptors rather than dopamine subtype 2 receptors. These drugs were synthesized in part by a chemist named Alexander Shulgin. He has written two popular books, titled Phenenthylamines I Have Known and Loved, as well as Tryptamines I have known and loved. These books contain “trip reports” as well as instructions on the synthesis of many phenethylamines and tryptamines. Their synthesis is extremely complicated and cannot be manufactured by clandestine labs as methamphetamine can.
The tryptamines act mostly on 5-hydroxytriptamine subtype 2A receptors and to a much lesser extent on dopamine subtype 2 receptors. They are stimulating and long-lasting, generally speaking. They include lysergic diethylamide (LSD, acid) as well as psilocybin (psychedelic mushrooms, ‘shrooms). It’s important to note that psilocybin is a pro-drug that converts to psilocin in the body. A pro-drug is a drug which is only active by metabolism in the body by enzymes. Another example of a pro-drug is diacetylmorphine (diamorphine, heroin). Heroine converts to morphine in the body, but diacetylmorphine is much more lipid soluble then morphine and crosses the blood-brain barrier quicker than morphine.
The opiates are a group of drugs that induce analgesia, euphoria, and sedation. They are physically addictive as well as psychically addictive. All opiates are synthesized from the alkaloids of poppy plants and include morphine, codeine, and thebaine. Opiates can be natural alkaloids, semi-synthetic and synthetic. Examples of semi-synthetic include hydrocodone (Vicodin, Lortabs), oxycodone (Oxycotin, Percocet), hydromorphone (Dilaudid), and oxymorphone. Semi-synthetic opiates are powerful drugs. There are many semi-synthetic opiates; too many to list. Synthetic opiates include the drugs meperidine (Demerol) and methadone, as well as many others. These drugs are mu-opioid agonists; some are mixed agonists/antagonist. There are also pure antagonists, such as naltrexone (Revia) and naloxone (Narcan). These drugs are used as an antidote to opiate overdose. They instantly antagonize the effects of opiates and bring the overdose victim out of the drug-induced coma and repertory depression. Recently, it’s been discovered that these opiate antagonists are somewhat effective as smoking cessation drugs. Side effects of opiate antagonists include major depression, since natural opiates which occur in the brain are responsible for well-being and sexual pleasure. These natural opiates include beta-endorphin and dynorphine, as well as other ligands.
There are 4 known subtypes of opiates in the brain: mu-receptors, delta-receptors, kappa receptors and sigma receptors. Mu-receptors mediate the pleasurable effects of natural, semi-synthetic and synthetic ligands. Delta-receptors cause the repertory depression of opiates and may play a role in the antidepressant qualities of opiates. Kappa-receptors and sigma-receptors are thought to be aversive. In fact, these subtypes are thought to be involved with dysthymic and major depression. There are other drugs which act on the opiate receptor of the sigma-subtype. These drugs include phencyclidine (PCP, angel dust), ketamine (Ketaset), dextromethorphan (Robitussin, Vicks 44), and dextrophan (a metabolite of dextromethorphan). These drugs belong to a group known as the disassociates. They also act on the N-methyl-D-aspartate receptors.
The minor tranquilizers include barbiturates and benzodiazepines. The barbiturates are separated into 4 groups: the long-acting barbiturates (Phenobarbital, Luminal), the moderate-acting barbiturates (butalbital, Fioricet, Fioricet), the short-acting barbiturates (amobarbital and secobarbital, found in a cocktail known as Tunial), and ultra-short acting barbiturates (thiopental). Thiopental is used in capital punishment by lethal injection and is meant to cause unconsciousness in the inmate by administering a massive dose before the pancurnium bromide and potassium chloride are given. These drugs are all given via I.V. There are arguments against the use of thiopental, as some people believe the drug doesn’t induce unconsciousness. This argument is likely unfounded since the dose (5 grams or 5000 milligrams) is massive and is likely to induce complete unconsciousness and severe repertory depression.
Another group of minor tranquilizers are the benzodiazepines. These drugs have largely replaced the barbiturates. Drugs of this class have five distinct properties: anxiolytic properties, myorelaxant properties, amnesic properties, anticonvulsant properties and sedative properties. They are largely used for each of these properties. Certain benzodiazepines lean towards specific properties. Diazepam (Valium) is used as an anticonvulsant and myorelaxan, alprazolam (Xanax) is used as an anxiolytic and in some cases as an antidepressant (although this is rare, but there is evidence that it does possess this property), temazepam (Restoril), flurazepam (Dalmane), and nitrazepam (Mogadon) are used as hypnotics, and clonazepam (Klonopin) is used as an anticonvulsant. There are more than 50 benzodiazepines that have been synthesized so far: Adinazolam, Alprazolam, Bentazepam, Bromazepam, Brotizolamz Camazepam, Chlordiazepoxide, Cinolazepam, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Cloxazolam, Cyprazepam, Diazepam, Doxefazepam, Estazolam, Ethyl loflazepate, Etizolam, Fludiazepam, Flumazenil, Flunitrazepam, Flurazepam, Flutazolam, Flutoprazepam, Gidazepam, Halazepam, Haloxazolam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Mexazolam, Midazolam, Nimetazepam, Nitrazepam, Nordazepam, Oxazepam, Oxazolam, Phenazepam, Pinazepam, Prazepam, Quazepam, Ro15-4513 (a research benzodiazepam that is not prescribed), Temazepam, Tetrazepam, Tofisopam, Triazolam, and Zolazepam.
The first benzodiazepine was synthesized by Leo Steinbach of Hoffman-LaRoch pharmaceuticals in the 1950’s. The company was searching for a drug that was safer than the barbiturates, as the group of drugs has extremely high dose-related side effects and can easily be lethal as well as the drug meprobamate, which is highly addictive. They began synthesizing random chemicals to meet the task of creating such a drug. One chemical, chlordiazepoxide, had been stored in a dusty corner of the lab. On a hunch, after two years of sitting in the lab, Leo tested the drug on monkeys and rats. He was amazed to find that the chemical had sedative and taming properties. It was discovered later that the drug was a result of a lab error by one of the chemists. The scientists were quick to synthesize an analogue of chlordiazepoxide, one that was more potent. The drug they came up with was christened diazepam and was given the name Valium. They were amazed at the effectiveness of diazepam in patients with nervous tension, and soon began to wonder what the big fuss over chlordiazepoxide was, since diazepam was much more effective than the drug.
18-06-2007, 00:51
Some Basic Pharmacology; cannabinoids, uppers, downers, and opioids
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