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

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If everyone else lacks a copy of that one massive chart with various stimulants' binding affinities and propensities to release monoamines, I can load mine up. Amphetamine is on there, I believe with double-digit affinities for DA and NA, and >1000 for 5ht.

ebola
 
ebola? said:
If everyone else lacks a copy of that one massive chart with various stimulants' binding affinities and propensities to release monoamines, I can load mine up. Amphetamine is on there, I believe with double-digit affinities for DA and NA, and >1000 for 5ht.

ebola
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Please upload it:D

I found this on wiki:
5HT2C receptors mediate the release of dopamine in response to many drugs,[6][7] including caffeine, nicotine, amphetamine, morphine, and many others.
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Apperantly some serotonin receptors play a roll in amphetamines dopamine release.
 
Here you go:

http://en.wikipedia.org/wiki/User:Rocknroll714/affinities

Apperantly some serotonin receptors play a roll in amphetamines dopamine release.
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The study cited there refers to cocaine rather than amphetamine.

Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence.

Bubar MJ, Cunningham KA.

Center for Addiction Research and the Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA.

The development of novel pharmacological agents for the treatment of psychostimulant use disorders is an important research imperative. One potential target system that has been largely overlooked is the serotonin (5-HT) neurotransmitter system. Preclinical studies indicate that 5-HT may be important in modulating the reinforcing properties of various drugs of abuse. While the potential sites of action of 5-HT within the brain are extensive, the natural starting point to examine the mechanisms by which 5-HT may be useful in treatment of psychostimulant use disorders is the interaction between 5-HT and dopamine (DA), a primary mediator of the "rewarding" effects of psychostimulants. Two key modulators of DA output are the serotonin (5-HT)2A receptor (5-HT2A R) and the 5-HT2C R. These receptors are known to control the neurochemical and behavioral effects of psychostimulants, and in particular, the in vivo effects of cocaine. Preclinical studies indicate that 5-HT2A R antagonists and/or 5-HT2C R agonists may effectively reduce craving and/or relapse, and likewise, enhance abstinence, while 5-HT2C R agonists may also effectively reduce cocaine intake in active cocaine users. At present, the progression of studies to probe the effectiveness of 5-HT2A R and 5-HT2C R ligands in the clinical setting is hindered by a lack of available selective 5-HT2A R antagonists or 5-HT2C R agonists for use in human cocaine abusers. However, a number of selective 5-HT2 R ligands currently under development, or in early clinical trials for psychiatric and/or neurological disorders, may soon be available for translational studies to explore their effectiveness in modulating drug use and dependence.
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You put it in an aqueous solution of sodium hydroxide and it precipitates out as an oil. That's it.

Amph-H+ + Cl- + OH- + Na+ -> Amph + H2O + Cl- + Na+
 
1) Would a SSRI prevent the neurotoxicity from methamphetamine?

2) Is it safe to combine an NRI with a NE releasing agent?
 
The neurotoxic effect of fluoxetine coadministered with methamphetamine is weird,
Fluoxetine increases long-lasting neostriatal dopamine depletion after administration of d-methamphetamine and d-amphetamine.

Ricaurte GA, Fuller RW, Perry KW, Seiden LS, Schuster CR.

Repeated administration of large doses of d-methamphetamine produce long-lasting depletion of brain dopamine (DA) and serotonin (5-HT), as well as persistent decreases in the activity of their respective biosynthetic enzymes, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH). The present results indicate that the inhibitor of 5-HT uptake fluoxetine, prevented the long-term depletion of 5-HT produced by large doses of methamphetamine (15 mg/kg X 5, 6 hr apart) in the neostriatum and hippocampus, while simultaneously augmenting the depletion of DA produced by this drug in the neostriatum. Fluoxetine also enhanced the prolonged neostriatal depletion of DA produced by a comparable regimen of d-amphetamine. In these doses (15 mg/kg X 5,6 hr apart), d-amphetamine did not produce long-lasting depletion of 5-HT in either the neostriatum or hippocampus. Larger depletion of DA after the amphetamines had been administered in the fluoxetine pretreated animal were associated with a transient increase in the brain levels of methamphetamine and amphetamine. This suggests that fluoxetine may inhibit the metabolism of amphetamines.
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2) It is safe, but the NRI cancels out the effect of the NE releasing agent on the NE. Not that that really matters, because the effects of NE generally aren't that desirable.
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They can be. MDMA is selective for NE over DA and N-Ethylcathinone is reported to be a likeable stimulant.
 
IIRC, MBDB hits NE rather prominently too, but not DA. So there's a step in teasing neurology ------> phenomenology.

However...do we have selective enough dopamine or dopamine and serotonin releasers to show whether stimulant and empathogen "likeability" depends somehow on release of NE?

And as I recall, a particular selective NE releaser was widely found not to be fun (forgetting what it was).

We could conduct a similar exploration of reuptake inhibitors...but blocking SERT seems to do something very different from release.

ebola
 
???

Hi i'm a newbie:P, i was wondering whether anybody out there can help, does anybody know, approximately, how many studies have been done with beta- substituted 2- phenylethylamines? xx
 
Just to clarify, as most of you probably know, serotonin decarboxylated to 5-hydroxytryptophan. Which is the active substance at the neurotransmitter sites.
It is degraded by MAO in the presynaptic cleft, so basically any drug that inibits reuptake prolongs the effects of serotonin.
As far as the specific receptors are concenened the most sedating one is the 5-HT 2a receptor, havent done enought experimenting / reading to fully understand the remainder of the receptors.
An additonal interesting fact about 5-HT drugs is that there is an autoreceptor (research is currently being done on how this works) it takes about two weeks for these autoreceptors to desensitize which means more effect of the drug, unless of course, they target other classes of neurotransmitters such as catecholamines. Prescription meds tend to work on both.
 
^My understanding, for pseudoephedrine at least, is that the direct affinity for NE receptors is quite weak/low. Ephedrine is different, it has significant direct agonist effects.However, to me it seems fairly irrelevant, as the overall action is still activation of the NE receptors. Ephedrine isn't that selective for NE however, it also releases some dopamine, and serotonin to a lesser extent.

Regarding n-Ethylcathinone, although this is a fairly selective NE releaser, it is metabolised to cathinone which has quite significant inhibition of dopamine reuptake.
 
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