Pharmacology - Nitrazepam (Mogodon)

[Jatelka]

Nitrazepam is 9-nitro-6-phenyl-2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen-3-one.

It has the chemical formula C15H11N3, and a molecular weight of 281.3.



It is a yellow crystalline powder which is insoluble in water, and soluble in alcohol, ether and chloroform. It has a melting point of 226-229 C.

Pharmacokinetics

It is well and fairly rapidly absorbed from the GI tract, when taken orally. Peak plasma concentrations occur at 2 hours (0.5 – 5 hours). Peak plasma levels following an oral dose of 10mg are 68-108ng/ml. 12 hours after oral administration levels are 12 – 38 ng/ml.

Bioavailability varies from 54% (oral) to 94% (iv). It is 87% protein bound.

It is metabolised I the liver to 7-aminonitrazepam and then to 7-acetamidonitrazepam, and is then hydroxylated. The metabolites are not thought to have significant pharmacological activity. Nitrazepam does not cause liver enzyme induction or inhibition with long term treatment.

Clearance is 4.1+/- 2 L/ hour , and 4.7 +/- 1.5 L/hour in the over 65’s.

It is mainly excreted as urinary metabolites, aprox 70% of a dose is excreted this way. Less than 1% is excreted unchanged.

Half life is 16-48 hours (mean 27).

From clinical studies: Nitrazepam is absorbed at variable rates, and there is a lot of inter-individual variation in peak plasma levels. It crosses the blood brain barrier, and is excreted in breast-milk.

Indications

It is licensed for use in (the short-term) the treatment of insomnia. Usual therapeutic dose is 5-10mg at night.

Contraindications

Hypersensitivity, Chronic/Severe respiratory disease, severe hepatic impairment. Caution is advised in renal impairment.

Interactions

There is an additive sedative effect with other CNS depressants (including alcohol). Because Nitrazepam undergoes oxidative metabolism drugs which reduce this (such as cimetidine and disulfiram) increase plasma levels. The anti-cholinergic effects of drugs such as antihistamines and some antidepressants are potentiated by Nitrazepam. Niytrazepam also interacts with some anticonvulsants.

Adverse effects

Anterograde amnesia (including complex behaviours such as sleep-driving and sleep-sex) have been reported. This can occur with normal therapeutic doses, and is more likely when the maximum dose is exceeded, or when it is combined with other CNS depressants. Somnolence and dizziness are common.

There have been rare reports of angioedema and anaphylaxis.

As with all benzodiazepines, physical dependence and withdrawal can occur with as little as 14 days continuous use. Nitrazepam should not be discontinued abruptly.

Other rare side effects include low blood counts and deranged liver function tests. Periodic blood monitoring is advised.

Nitrazepam (and other benzodiazepines) may increase depression, and are not recommended as first line treatment. They can also worsen confusion and psychotic symptoms in schizophrenia and mania. Suicidal tendencies may be unmasked.

Paradoxical reactions (agitation, hallucination and aggression) may occur.

Use in Pregnancy

Is not recommended, and neonatal withdrawal symptoms have been reported. Foetal abnormalities have been demonstrated in studies with other benzodiazepines in the first trimester. Nitrazepam is excreted in breast milk, and should not be used by nursing mothers.

[tranquillike]

Anyone with a story or input on nitrazepam? SWIM is very curious about this one, but it seems to be rather scarce... both in supply and information. SWIM finds hypnotics rather enjoyable. How does nitrazepam compared to other typical hypnotics?

Reputation Comments on this post:

yah, i was wondering the same thing. welcome

[all_time_high]

This thread might help you http://www.drugs-forum.com/forum/showthread.php?t=30774

its a benzodiazepines which is very similar to Diazepam(valium) in its effect. SWIY should start with 20mg to see how it reacts to you. Its a very addictive substance and may lead to life threatning situations in sudden withdrawals.

SWIm generally does 70-100mg and feels really good for next 7-8 hours. But this is a very high dosage which can even be fatal and not at all recommended to beginners.

[Psych0naut]

Originally Posted by all_time_high

This thread might help you http://www.drugs-forum.com/forum/showthread.php?t=30774

its a benzodiazepines which is very similar to Diazepam(valium) in its effect. SWIY should start with 20mg to see how it reacts to you. Its a very addictive substance and may lead to life threatning situations in sudden withdrawals.

SWIm generally does 70-100mg and feels really good for next 7-8 hours. But this is a very high dosage which can even be fatal and not at all recommended to beginners.

It's certainly not fatal in such a dose. Benzodiazepines are known for their high safety profile. People have tried to commit suicide by gobbling a few hundred pills, and all they did was sleep for a few day's, but woke up just fine. It's another story when it's combined with other depressants, like alcohol. And some of the strongest benzodiazepines, like Dormicum(midazolam) and Halcion(triazolam) might cause death as well, when taken in very high doses.

[tranquillike]

SWIM has read that triazolam is one of the more dangerous benzos... not sure what it is about it, but extra caution should be advised with this one. SWIM doesn't really know anything about midazolam other than it is typically used for pre-op

Reputation Comments on this post:

that is a good point

[Laudaphun]

So would Nitrazepam be considered the next step up from temazepam when it comes to hypnotic benzos or would temazepam be considered more effective? Or does the u.S. even have nitrazepam on the market. This is a benzo that SWIM has never seem or heard anyone talking about.

[tiramisu4you]

SWIM took 10mg each night for two weeks. SWIM got no sleepiness or euphoria from Nitrazepam. SWIM thinks Nitrazepam sucks. Now SWIM takes 2mg of flunitrazepam and that knocks him out like a baby. SWIM would never take a hypnotic benzo in public, it would just make him sleepy.

[zapatista]

pacidrims ( mexican version of nitrazepam) were quite popular in the border(us/mex) areas back in the 80's. SWIM thinks they were great. All of a sudden, rohypnol became more popular and pacidrims were yesterdays news.
Common problem in an area where downers are easily available. Swim can list them all:
optanox,nubain,pacidrim, mandrax,valium, tafil(sic), ativan,percodan,turbogesic and any youcould think of as long as you had 10.00$ for a script.

[RoboCodeine7610]

Over here in Saudi, this is a very commonly abused drug and goes by the name of "Gueshta" literally translated meaning "cream".Swim personally hates any drug that induces severe memory loss and the first and last time he tried a benzo (Clonazepam, ~4mg-5mg) he stole a car and got arrested so he's never touching that shit gain...

[Laudaphun]

SWIM would like to hear some accounts of people who have been familiar with benzodiazepines as a whole and are able to compare and contrast the effects of nitrazepam with other more common benzos. Aside from temazepam, nitrazepam is the only other benzo approved for use in the U.S. which is considered a hypnotic benzo as far as SWIM knows. (No we don't have flunitrazepam available legally in the U.S.) Other benzos may be prescribed for sleep but not necessarily be hypnotics. Midazolam is available only in the form designed for parenteral use so while it's use is as a hypnotic during surgery, we do not have any pill form of the drug.

[RoboCodeine7610]

I thought any benzo was a hypnotic in a high enough dose right?

[Laudaphun]

I suppose you could look at it that way, however from a pharmacological point of view, benzos typically fall into one or more of the following 3 categories: anxiolytic, anticonvulsant, and hypnotic. This may differ from country to country but different benzos are considered to be categorized as hypnotics, anxiolytics, or anti-convulsants. This depends on their primary action. Clonazepam for example is used as an anxiolytic in the U.S. whereas in the U.K. I think it is strictly used in cases of status epilepticus. Would have to double check on that with some folks living over their though.

[Jatelka]

^^^ Clonazepam is used in epilepsy here, yes. But it's generally rectal Diazepam or iv Lorazepam for status, with Clonazepam more used for stable disease

[RoboCodeine7610]

I suppose you could look at it that way, however from a pharmacological point of view, benzos typically fall into one or more of the following 3 categories: anxiolytic, anticonvulsant, and hypnotic. This may differ from country to country but different benzos are considered to be categorized as hypnotics, anxiolytics, or anti-convulsants. This depends on their primary action. Clonazepam for example is used as an anxiolytic in the U.S. whereas in the U.K. I think it is strictly used in cases of status epilepticus. Would have to double check on that with some folks living over their though.

Right, so they're classified by their strongest action?I mean what does "Main action" mean?They're all hypnotics, anxiolytics, and anti-convulsants right?

Perdon me as I really don't know that much about benzos...

[Laudaphun]

Originally Posted by RoboCodeine7610

Right, so they're classified by their strongest action?I mean what does "Main action" mean?They're all hypnotics, anxiolytics, and anti-convulsants right?

Perdon me as I really don't know that much about benzos...

Well, they are classified however the government of your country decides to classify them. There are a lot of benzos that we don't even have in the U.S. that are in common use in other countries. Nitrazepam is one of the benzos used in SWIM's country that she has never encountered nor heard any talk about. Sorry to confuse you, SWIM was just basically trying to "stir the fire" and see a good report or two posted on nitrazepam.

[RoboCodeine7610]

Well, they are classified however the government of your country decides to classify them.

So it's not a pharmacological classification right?It's just a legal status basically,ok.Swim just didn't understand it from a pharmacological point of view cause they all do all 3 things.

Thanks for the clarification,

Robo

[tyranny4u]

SWIM doesn't get any euphoria or any other nice high from Nitrazepam.
Also it's hypnotic potency is not that strong. Nitrazepam takes quite long
to come in (up to an hour). SWIM thinks it's a "better to have this than
to have nothing benzo"
Chemically Nitrazepam is very close to Clonazepam:



you see, they are similar besides the chlorine atome attached to the
phenyl group, this makes the drug more potent. actually this should
make Clonazepam more hypnotic than Nitrazepam, but doesn't. an ex-
ception to the rule...
SWIM thinks some people might overrate this drug because of the name
which is close to Flunitrazepam. But forget it ;-)

[Laudaphun]

If i had to guess, flunitrazepam has just a flourine molecule attached someone where instead of chlorine on clonazepam? just off the top of my head i'd guess there is a flourine group attached to it. Assuming that is correct, that electronegativity of flourine would perhaps be the what makes it so strong? SWIM really doesn't get effects other than therapeutic. It is surprising that no one really seems to enjoy nitrazepam, SWIM just assumed it would be very similar to temazepam. Which was her favorite from times past. Now, they do not give any type of "recreational" feeling so now she'd probably say it wasn't very good. Temazpam is the only hypnotic benzo SWIM has ever got to try, and that just reminded her marmoset of something her counselor said... The nice dr. goes away. Well, to sum it up, the person that took over, just left SWIM on them. And, it was the only benzo that SWIM really felt cravings for. But for a long time SWIM didn't have access to much else, dr. would give only chlordiazepoxide which was useless in her case. Eventually, SWIM began taking alprazolam, and while she never developed the cravings for it that she did for temazepam, it put her temazepam usage back at reasonable levels. Just curious if other short-acting, hard hitting benzos (or what you might consider a hypnotic) were similar.

EDIT: SWIM just re-read her post and started thinking of other halogens, bromine is next below chlorine. Bromazepam, which is not use in this part of the world, so another benzo swim knows little about, other than what's written in books. So is nitrazepam the base model for several mono-halogenated benzos? Well analogs I guess. SWIM doesn't really know but is typing before going for the chemistry book.

[tyranny4u]

If i had to guess, flunitrazepam has just a flourine molecule attached someone where instead of chlorine on clonazepam?

no, it also has a methylene group next to the first nitrogene in the ring.

have a look here:
http://www.drugs-forum.com/forum/showthread.php?t=80291

Reputation Comments on this post:

interesting info.

[Laudaphun]

Originally Posted by tyranny4u

no, it also has a methylene group next to the first nitrogene in the ring.

have a look here:
http://www.drugs-forum.com/forum/showthread.php?t=80291

That's interesting, and well explained. I'll have to get back and look over this better. I never realized how subtle the differences between those drugs really were. Very cool. There's lots of stuff I'd like to do, but time always limits a lot. But I think it would be cool to have a nice neat grouping of different classes of medications showing the diffferents. Is there some health concern about meds that contain halogens? Maybe it was only one specific one, but I could have sworn I was just reading a paper that advised avoiding certain meds for the simple fact they had a F or Cl atom. Of course I think it might have also advised that it was bad to have that stuff in drinking water as well.

For some reason I was thinking Nimetazepam was THE benzo, but relly only avail on the black market in (Asian? Countries) I think I had read that Nimetazepam comprised 85% and Temazepam comprised 15% of the illicit benzos on the market by organized crime.