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Advanced Opiate/oid Pharmacology

A

AlphaMethylPhenyl

Moderator: TDS
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I know that opiates/oids act in the same way as endorphin/enkephalin/dynorphin but all save for once what I've heard is mu, delta, and kappa, as well as dopamine, and oh, that it decreases norepinepherine. Once I came across something that states opiates also increase serotonin. Does anyone know what sub-types of dopamine/serotonin is increased by opiates and where, also how this compares to other drugs of "abuse". I know its never so simple as nuerotransmitter x fires.

I actually just want a to know the comprehensive pharmacology.
 
Well, besides the obvious serotonin effecting opiates like tramadol/tapentadol I remember reading a report of Oxycodone causing serotonin syndrome in combination with an MAOI, maybe that's why oxycodone is less sedating? Demerol does something to serotonin too.

Salvia is a kappa-opioid agonist, and they tend to cause dysphoria and hallucinations(which salvia is known for).
 
Thanks sekio

Wait so a selective agonist at mu-1 wouldn't create physical dependence?

And cool I didn't know dynorphin is an agonist at mu too.

From what I understand opiates inhibit gaba, thus increasing dopamine. That's strange though because gabaergics are thought to be recreational, though not as much as opiates. Oh yeah, its never so simple as nuerotransmitter x...blah blah.

And opiates overall are NMDA antagonists?

It looks like in figure five there is interaction with the nicotinic receptors.
 
i just figured that when they attach to opiate receptors it's like the missing puzzle peice that makes you feel great.

I thought they released dopamine not seretonin but idk
 
There's a study that came out recently saying the dopamine release might actually be from an immune response and blocking this response could prevent addiction (By making them not as pleasurable)
 
So if opiates inhibit GABA, how come they seem anxiolytic to me? (And I don't hear many, if any reports on opiates giving anxiety)
 
Well anxiolysis can be caused by many mechanisms: serotonin re-uptake inhibition, 5-HT1 agonism, GABA release/potentiation, and even the potent dopaminergic action of stimulants such as amphetamine.
 
Ho-Chi-Minh said:
Well anxiolysis can be caused by many mechanisms: serotonin re-uptake inhibition, 5-HT1 agonism, GABA release/potentiation, and even the potent dopaminergic action of stimulants such as amphetamine.
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But opiates INHIBIT GABA, and if an increase of GABA causes anxiolysis, shouldn't a decrease cause anxiogenesis(not sure if that's a word.)? (I'm not saying you're wrong about them inhibiting gaba, I'm honestly curious how this doesn't cause anxiety like a GABA antagonist will) about And I find amphetamines to be the best thing for social anxiety, as it gives me confidence so that I don't worry about rejection. Anxiety due to anything that isn't social though it doesn't effect negatively or positively. Unless you count the paranoia I get after being awake for days.
 
i'm not much use for advanced discussion of opioid pharmacology but i don't find opiates to be the greatest anxiolytics. If i'm nodding out then they are but that's because i'm not thinking of anything. Maybe it's the dopamine release that relieves anxiety, in a similar way to amphetamine. Opiates are great for social anxiety and so are amphetamines so i think that makes sense. I think there might be a connection between analgesia and anxiety as well.

I also read that dopamine gets broken down into norepinepherine which is a likely reason opiates can cause panic attacks in some individuals.

I believe cannabis also inhibits gaba but can still provide anxiolytic effects for some people. For others this just leads to anxiety. It probably depends on the individual's chemistry. Those with ADD and social anxiety may benefit more than someone with panic disorder.
 
Jackie I'm sure people would agree that an opiate and a gabaergic drug is more anxiolytic than just an opiate. Basically the anxiolytic effects of mu/delta agonism would outweigh a marginal inhibition of GABA; that is, usually.
 
endotropic said:
Wait a minute, I thought the idea of multiple u/d/k subtypes (mu1, mu2, etc.) was a bit outdated at this point. I certainly don't see anyone discussing subtypes in current literature. Hasn't this been disproven?
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IIRC there are different receptor variants, not too sure on the implications though, I do way way too much cardiac pharmacology
 
JackiesBabyy said:
So if opiates inhibit GABA, how come they seem anxiolytic to me? (And I don't hear many, if any reports on opiates giving anxiety)
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I'm pretty sure opiates have pro-GABAneric effects, and for the most part, exhibit a cross-tolerance with benzodiazepines.
 
I think what people forget is that when people say "opioids increase GABA transmission" they mean in some localities of the brain, not as a global effect.
They sure as shit don't exhibit proper cross tolerance with benzodiazepines.
 
Ho-Chi-Minh said:
Jackie I'm sure people would agree that an opiate and a gabaergic drug is more anxiolytic than just an opiate. Basically the anxiolytic effects of mu/delta agonism would outweigh a marginal inhibition of GABA; that is, usually.
Click to expand...

Well, hey, I'm learning :P So are the effects of opiates attributed to delta agonism too? I haven't heard much about the delta opioid receptors but have read about how exactly the mu receptors are what causes both euphoria and pain killing properties. What roles does delta play here?
 
Epsilon Alpha said:
IIRC there are different receptor variants, not too sure on the implications though, I do way way too much cardiac pharmacology
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Yup. There are many many different variants. Here's a great paper that details some mu alternative splicing variants, but mostly focuses on one. The coolest part is that it's a functional 6 transmembrane GPCR! Gavril Pasternak is involved with a lot of mu receptor variants/splicings if you want to learn more.

Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects.
Pain remains a pervasive problem throughout medicine, transcending all specialty boundaries. Despite the extraordinary insights into pain and its mechanisms over the past few decades, few advances have been made with analgesics. Most pain remains treated by opiates, which have significant side effects that limit their utility. We now describe a potent opiate analgesic lacking the traditional side effects associated with classical opiates, including respiratory depression, significant constipation, physical dependence, and, perhaps most important, reinforcing behavior, demonstrating that it is possible to dissociate side effects from analgesia. Evidence indicates that this agent acts through a truncated, six-transmembrane variant of the G protein-coupled mu opioid receptor MOR-1. Although truncated splice variants have been reported for a number of G protein-coupled receptors, their functional relevance has been unclear. Our evidence now suggests that truncated variants can be physiologically important through heterodimerization, even when inactive alone, and can comprise new therapeutic targets, as illustrated by our unique opioid analgesics with a vastly improved pharmacological profile.
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http://www.ncbi.nlm.nih.gov/pubmed/22106286
 
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