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The Large and Nifty Not-quite-advanced Drug Chemistry, Pharmacology and More Thread

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Yohimbine is a 5-HT1A, 5-HT1D, and 5-HT2A agonist and a 5-HT1B, 5-HT2B, and alpha 2 adrenergic receptor antagonist.

When I take yohimbine, I feel excruciatingly bored, aboulic, and anhedonic (or more so than usual anyways), but when it wears off, I feel quite blissful and sociable. It seems to be that its anti-depressant effect lies within its rebound effects - at least for me.

The other day I conducted a little, fairly risky experiment wherein I took 50 micrograms of clonidine with 500 or 1000mg of Yohimbe bark powder every half an hour for two hours and threw in a few hundred milligrams of 5-hydroxytryptophan for good measure. I felt better the next day than I had in years. (5-HTP alone makes me feel worse, so it probably wasn't that.)
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The fact that Yohimbine HCl, and especially the sum of Yohimbe bark hits those 5-HT receptors does make it an imperfect tool for gauging a2 behavioral and cognitive response. That's why I'm in search of people who have experienced highly selective a2 antagonists in my other Yohimbine discussion here:
http://www.bluelight.ru/vb/showthread.php?t=433550

Anyway, it's funny that you attribute Yohimbe's 5-HT action to its antidepressant action. Reading your experiment, the first thing I would guess is that the rebound effect is due to the absence of Clonidine the next day, but that of course is not the case. I think both scenarios are possible in different individuals; I also find Cholinergics to have an antidepressant quality, while many people find anticholinergics -in moderation- to be euphoric.
 
shibireru said:
Yohimbine is a 5-HT1A, 5-HT1D, and 5-HT2A agonist and a 5-HT1B, 5-HT2B, and alpha 2 adrenergic receptor antagonist.

When I take yohimbine, I feel excruciatingly bored, aboulic, and anhedonic (or more so than usual anyways), but when it wears off, I feel quite blissful and sociable. It seems to be that its anti-depressant effect lies within its rebound effects - at least for me.

The other day I conducted a little, fairly risky experiment wherein I took 50 micrograms of clonidine with 500 or 1000mg of Yohimbe bark powder every half an hour for two hours and threw in a few hundred milligrams of 5-hydroxytryptophan for good measure. I felt better the next day than I had in years. (5-HTP alone makes me feel worse, so it probably wasn't that.)
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I think you have agonist and antagonist messed up. I thought it was the other way around. It antagonizes those 5-HT receptors, and increases activity or noradrenaline, dopamine, and nitric oxide.
 
Tsukasa-

Well, it most certainly does increase synaptic noradrenaline levels, since it is an alpha 2 antagonist. It is not, however - assuming that what I've read is correct (and it may very well be incorrect as you know) - a dopamine agonist, but rather an antagonist at certain dopamine receptors. Which it antagonizes specifically I'm not sure.

I don't know anything about its effects on nitric oxide levels.
 
acetylcholine said:
Reading your experiment, the first thing I would guess is that the rebound effect is due to the absence of Clonidine the next day, but that of course is not the case. I think both scenarios are possible in different individuals; I also find Cholinergics to have an antidepressant quality, while many people find anticholinergics -in moderation- to be euphoric.
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Yes, I utterly despise anything significantly noradrenergic or adrenergic. On the other hand, I don't especially like adrenergic antagonists either (*). My favorite substances are those which produce minimal effects of adrenergic/noradrenergic currents.


* Interesting story: I almost died from a labetalol overdose last night. I took a fairly typical dose after I had eaten, which is something I have never done before: evidently taking it on a full stomach vastly increases bioavailability. I took it for the purpose of maintaining normal sypathetic tone in the face of large doses of phenylethylamine. When I perceived various symptoms of overdose, including dyspnea, dizziness, bradycardia, and hyptension, I did everything I could to reverse this condition, taking significant quantities of amphetamine, salbutamol, and more phenylethylamine; but nothing worked! My heart rate rose only to 60 bpm and I was still hypotensive. To make matters much more frightening, my autonomic nervous system seemed to be gravely malfunctioning: I realized that if ever I ceased to consciously focus on breathing, my breathing would stop. At various points in the evening I would go 30 seconds or more without breathing and without experiencing any air hunger whatever. So I had to stay up until the labetalol had mostly worn off.

Scary shit! (Not dying but the thoughts of living as a vegetable)
 
evidently taking it on a full stomach vastly increases bioavailability
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First of all, gald you're okay. Scary shit indeed, but informative. I sometimes function under the same impression that all substances work more strongly on an empty stomach. This is not always the case, apparently with catastrophic results.
I did everything I could to reverse this condition, taking significant quantities of amphetamine, salbutamol, and more phenylethylamine
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I know the feeling. I have, due to poor judgement, had times when I've ingested too much of an anticholinergic substance, either for the purpose of treating severe nausea or motion sickness, or long in the past as pure experimentation. The nasty anticholinergic syndrome would linger into the next day and I would try every cholinomimetic drug I had to reverse the condition: huperzine, donepezil, carnitine, indirect releasers of acetylcholine, nothing would help. It's as if those stubborn muscarinic receptor blockers refused to budge.
 
shibireru said:
Tsukasa-

Well, it most certainly does increase synaptic noradrenaline levels, since it is an alpha 2 antagonist. It is not, however - assuming that what I've read is correct (and it may very well be incorrect as you know) - a dopamine agonist, but rather an antagonist at certain dopamine receptors. Which it antagonizes specifically I'm not sure.

I don't know anything about its effects on nitric oxide levels.
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I think i may have yohimbine mixed up with something else, or i've read incorrect information, sorry about that. Though reading up on it from a more reliable source, i see it's only a weak partial agonist at 5-HT1A, 5-HT1D, and 5-HT2A, not a full agonist.
 
Does BZP have any analgesic action?

PS: This topic should prolly be sticky'd.
 
to sound like an idiot or to not sound like an idiot...oh dern im already posting

Benzos/alprazolam + ethyl alcohol:

Is there any reasonable explanation to why when I take a low-moderate benzo dose(1-2mg alprazolam) with or without tolerance an hour or so before I start drinking that by the end of the night I am not drunk? I do drink less, but not that much less - and not because i am getting wasted. Im just being cautious. Then if i try to get wasted and succeed i dont end up blackout status...just normal wasted.

For me, it seems harder to feel the effects of alcohol when on benzos. The other night I had 1mg alprazolam before drinking and 2x redose at .5mg during alcohol consumption. I ended up drinking 5-7 16oz 5% etoh beers and then more than a few big swigs of wine. The people i was with were reasonably intoxicated, i was not.

In previous experiences with alprazolam and alcohol as the day turns to night I end up thinking "Wtf...benzos seem to just block all the bad effects of alcohol and make my benzos work better." It really feels like when i drink moderately on a reasonable (2mg MAX) dose of alprazolam that all the alcohol does is make the benzos kick in harder. I dont end up stumbling or pass out.

Today i took 1mg alprazolam, and then a half our later 32 oz of beer on a near-empty stomach and didnt feel anything past the benzos kicking in. ??

From past experience ive noticed my brain and or my drug metabolism is way drifferent than anyone I know except some family. Drugs in general last longer on me, and pot for example does the exact opposite of what most stoners get from it. Instead of relaxation i get stimulation, etc. Im a bit hypersensitive to all stimulants. Hydrocodone can last for up to ten hours on me. I'm always the last guy awake cracked out on acid...etc.

Also on that note, generally when im sober a beer wakes me up, and if I am anxious alcohol actually seems to worsen it or do nothing but make me feel like shit.

Anyway...I am looking for any type of pharmacological insights on the alprazolam and alcohol thing. I was thinking that since apparently ethyl alc is a gaba-a agonist yet binds at a different site on the receptor protein maybe that has something to do with it? I really dont know...hoping someone will.

Maybe i just think I'm not drunk but am? I really dont think thats the case as in situations described above i end up driving people completely straight, yet maybe over the legal BAC, at the end of the night when theyre all goofed out from the same amount of booze ive had and could never drive.

enlighten me, shame me, whatever, like arnold said...DO IT!!!!
 
If I'm not mistaken, alcohol has important effects involving benzodiazepine binding sites, a1 or 2, primarily, no? I believe alprazolam has highest affinity for a1 subunit containing GABA-A receptors.
 
How likely is it that serotonin syndrome should occur following the administration of these combinations of serotonergics:

1. 5mg of Pindolol (Unlike certain other beta-blockers, it's an antagonist at the 5-HT1A autoreceptors only... supposedly) + 100mg of Nefazodone (SNRI, 5-HT2A antagonist, and alpha 1 antagonist) + 100mg of 5-HTP

2. 5mg of Pindolol + 100mg of Nefazodone + 10mg of Citalopram

3. 5mg of Pindolol + 10mg of Citalopram

Is any of these acceptably safe? I'm thinking that only the third is - if that.

I've been taking Pindolol and Nefazodone for the past three days and I feel like garbage. I had had such high hopes that I had finally found a winning combination, but so far (granted it's too early to be drawing any sound conclusions) it's looking like I'll never get better. This was pretty much my last attempt. I've already tried dozens of medications and nothing's worked. Fuck this!
 
mr.dopeman said:
Does anyone know the solubility of THC and other cannibinoids in solvents such as ethanol, isopropyl alcohol, and acetone. And specifically at spefcific temepratures. Are Thc and any other of the cannibinoids insoluble in any of those solvents at a temeprature achivable in a freezer?
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Probably not. I think the solubilities are too high to get any one of the cannabinoids to come out of solution. You're also trying to isolate a compound from a mixture of similar compounds that are capable of solubilizing each other. When you concentrate the solutes, you inevitably end up with an oil.

One strategy might be to modify the solubilities of the cannabinoids by derivatizing them. You can isolate CBN-acetate after reaction of hemp oil with acetic anhydride. The hydrolysis of that isolated product gives cannabinol.

Could make the 3,5-dinitrobenzoate ester derivative by reaction with 3,5-dinitrobenzoyl chloride in pyridine....or the 3,5-dinitrophenylurethane derivative by reaction with 3,5-dinitrobenzoyl azide.

A more recent patent suggests replacing the azide with an isocyanate to make the crystallizable THC carbamate that could be hydrolyzed back to THC.
 
In the Antidepressants and Recreational Drugs (long!) FAQ there is the claim that mirtazapine potentiates hallucinogens like LSD. But to my knowledge (I could be wrong) mirtazapine is an antagonist at 5HT2a and the hallucinogenic effect of LSD is very often attributed to LSD being a 5HT2a agonist. And 5HT2a antagonists blocks the hallucinogenic effect of LSD.

Why then does mirtazapine potentiate LSD?
 
Today at 10 am I took one 36 mg Concerta (methylphenidate OROS formulation). Will the EFFECT still be there at all at 4 pm tomorrow?
 
Probably not. The extended release tablets are designed to progressively release the drug throughout the day but still allow sleep at night.
 
Would selegiline be useful for making the day after MDMA more bearable, or would it simply slow the catabolism of alpha-methyl-dopamine, making the crash worse?
(note, I am not saying that selegiline should be combined with MDMA).

ebola
 
alpha-methyl-dopamine's biggest issue is the gluconuride metabolites (I think I have that right, it is amDA's metabolites that's the problems). I don't know if it's targeted by MAO, but if it is, then yeah, if you block that metabolic route, then more will be turned into the gluconuride.

I doubt it'll do anything beneficial for the crash though.

Also, unless you take a pretty high dose, it won't have much in the way of beneficial effects on 5HT.

Personally, I'd be worried about remaining MDMA and other metabolites causing problems if you block DA metabolism, because you'll be taking it fairly soon after taking the MDMA I assume.
 
Does activation of both the D1 and D2 DA receptor subtypes/classes suppress prolactin then? My thinking was that, even if this were the case, antagonizing D2 (which are primarily presynaptically located, no?) would increase DA substantially enough to offset this effect by stimulating D1 as well. Some people find low dose (i.e., D2 specific) amisulpride quite stimulating; even comparable to methylphenidate.

I ask because I'm thinking about trying low-dose amisulpride, possibly with a bit of l-deprenyl, for anxiety/depression and am trying to figure out whether any anti-psychotic-like side-effects are likely to occur due to prolactin increase.
 
rocknroll714 said:
Pindolol isn't a selective autoreceptor ligand nor is it a proper antagonist. It affects both autoreceptors and post-synaptic receptors just like any other ligand and it has about 20% intrinsic activity for activating the 5-HT1A receptor making it a weak partial agonist.

Also serotonin syndrome results from combined and excessive 5-HT1A and 5-HT2A activation. 5-HT2A antagonists (like nefazodone) diminish symptoms and have even been used to treat it.

For these reasons, I'd imagine those combinations would be relatively safe. You need pretty high levels of serotonin to cause serotonin syndrome anyway. I've taken.. 1 gram of 5-HTP without any ill effects (cept nausea) and 20 grams of L-tryptophan without any issues either (cept even worse nausea). I've taken 100 mg of paroxetine acutely with no indications of serotonin syndrome either. From what I hear you need something like 300 mg/kg of an SSRI for it to be fatal.
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Thanks for the response.

I am aware of much of that, but things are perhaps not quite so simple.

Firstly, Nefazodone is a NRI meaning that it could well exacerbate serotonin syndrome or make it more liable to occur. Secondly, it is presumably an antagonist at 5-HT2A autoreceptors as well as post-synaptic 5-HT2A receptors and in this it perhaps has a proclivity to dispose a person taking it to the development of the condition just as much as it has the capacity to mitigate or prevent the condition (depending on the density and sensitivity of 5-HT2A receptors, pre-synaptic and post-synaptic, of the individual taking it). Thirdly, I've read reports about it being one of the serotonergic medications most liable to cause serotonin syndrome. And then on top of all this, it is an SRI, which of course isn't a good thing as far as serotonin syndrome prevention is concerned.

P.S.

I read your post in which you first reported having taken a gram of 5-HTP and suffered no untoward effects. Though I knew that this wasn't particularly good for the heart, I decided to personally reprise this act: like you I took a whole gram of 5-HTP, but, unlike you, I had a shitty-ass time. I felt psychotic and just weird as all hell. No euphoria. (For the love of god why can't substances affect me positively the way they do for others!? Nothing makes me feel good.)

Just thought I'd share that.
 
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