Amisulpride and Opiate receptors

[jasoncrest]

From Biopsychatry.com:

Antinociceptive effects of various neuroleptics in animal acute pain-models have been described, mediated trough different pathways including the opioid system. In this study, we assessed the antinociceptive effects of the atypical neuroleptic drug amisulpride, which acts as a selective blocker of dopamine D2 and D3 receptors. Furthermore, at low doses amisulpride has a selective preference for presynaptic dopamine autoreceptors, while at high doses it manifests a preferential action at post-synaptic dopamine receptors. We found amisulpride to be a potent antinociceptor agent in the mouse tail-flick assay, with an ED(50) of 36.6 mg/kg. This effect was antagonized by naloxone (P<0.05), indicating an involvement of opioid mechanisms as mediators of the antinociceptive effect of amisulpride. beta-Funaltrexamine (mu(1)- and mu(2)-opioid receptor antagonist), naloxonazine (selective mu(1)-opioid receptor antagonist), naltrindole (selective delta-opioid receptor antagonist), Nor-binaltorphamine (kappa(1)-opioid receptor antagonist) reversed amisulpride antinociception at the same dose that they antagonized morphine's antinociceptive effect (all P<0.005). We found that the sensitivity of amisulpride-induced antinociception is mediated through selective involvement of all three opioid receptor subtypes. Based on previous studies with risperidone, clozapine and olanzapine we tend to attribute this global interaction with the opioid system to amisulpride's action at the dopamine D2 receptor sites.

So Amisulpride plays a role on mu, delta and kappa receptors.
If its effects are antagonized by mu, delta or kappa receptors, this mean that Amisulpride is a mu, delta and kappa agonist, that's right?

If Amisulpride plays a role on the 3 main Opiate receptors, does it have other effects besides analgesia? (euphoria?)

 

[IHateOpiophobes]

"The effect of the hallucogenic plant Salvia Divinorum and its primary active chemical Salvinorin-A can be inhibited by the pre-administration of naloxone, as well as PCP, ketamine, and dextromethorphan"

http://en.wikipedia.org/wiki/Naloxone


My guess is that if they are antagonised by naloxone etc.....then they must have some sort of action in the opiate systems. Obvioulsly, duh, but they must activate all of the delta, and kappa receptors too a much higher level, creating non-recognizable "effects" created by agonist activity other than on the mu receptor. Kappa receptor agonism only is supposedly very dysphoric.

As Im sure you know, opiates pleasurable well known effects are due to mu activity. So these other drugs work on different receptors creating different effects.

As far as Amisulpride is concerned, if it acted enough on the mu receptor in humans at least then it would probably be considered an opiate drug. If it does act on the mu, then my guess is that it is very small, therefore no medicinal use, so you don't hear about it very much. At least I haven't heard anything about Amisulpride.

Im not quite sure I understood your question correctly, but Im curious to learn anything I can about opioid receptor interactions. Maybe if Im way off you could try and explain a little further in detail.

 

[jasoncrest]

Amisulpride gives antidepressants effects when taken in low doses (50mg).
The explaination is that at lower dosages, Amisulpride enhances Dopamine release...
But maybe this explaination is false, and the antidepressants effects of Amisulpride are due to its Opiate-like effects? That would be interesting...

 

[benzofan]

Amisulpride gives antidepressants effects when taken in low doses (50mg).
The explaination is that at lower dosages, Amisulpride enhances Dopamine release...
But maybe this explaination is false, and the antidepressants effects of Amisulpride are due to its Opiate-like effects? That would be interesting...

I was under amisulpride in low dose (50mg/day) and it was fantastic for my SAD (negative syndrom, social withdrawl...)
But the effects tends to pop up after a few months (3-4) I don't understand why (tolerance ??, not sure at all...). And you cannot go over 100mg a day because the effect will be different (you will fell too speed, very difficult to fall asleep at night without an hypnotic drug). I'd switched to venlafaxine (awfull drugs) I prefer now Tramadol (even you can be quickly addicted)

NOTE : At 400mg/day (or more) amisulpride is used for postive syndrom only (hallucinations,...)

Then yes at low dose it is a little bit comparable to light opiates like tramadol (but without addiction)
A Reason of the anti depressant effect is also that amisulpride has ISRS properties + Dopamine release

 

[atara]

Amisulpiride demonstrates affinity for the GHB receptor and antagonism at 5-ht7. The former is associated with "happy" effects.

I'm tempted to believe the researchers:

Based on previous studies with risperidone, clozapine and olanzapine we tend to attribute this global interaction with the opioid system to amisulpride's action at the dopamine D2 receptor sites.

i.e. it acts as an opioid agonist only indirectly via allowing the release of beta-endorphin, which is apparently blocked by D2 activation.

 

[benzofan]

Sorry I made a big mistake in my post :

I said amisulpride has ISRS properties : it is completely wrong. I wanted to say :

Tramadol has ISRS properties

Amisulpride has Dopamine release properties

That's one of the reason they have both anti depressant effects

 

[benzofan]

Let's go in details :

Amisulpride shows a unique therapeutic profile being antipsychotic, at high doses, and disinhibitory, at low doses (anti depressant effect, euphoria, well being sensation,...), while giving rise to only a low incidence of extrapyramidal side effects. In vitro, amisulpride has high affinity and selectivity for the human dopamine D2 (Ki = 2.8 nM) and D3 (Ki = 3.2 nM) receptors. Amisulpride shows antagonist properties toward D3 and both pre- and postsynaptic D2-like dopamine receptors of the rat striatum or nucleus accumbens in vitro. At low doses (< or = 10 mg/kg) amisulpride preferentially blocks PRESYNAPTIC dopamine autoreceptors that control dopamine synthesis and release in the rat, whereas at higher doses (40-80 mg/kg) postsynaptic dopamine D2 receptor occupancy and antagonism is apparent.
Amisulpride is clearly a specific dopamine receptor antagonist with high and similar affinity for the dopamine D2 and D3 receptor. In vivo, it displays a degree of limbic selectivity and a preferential effect, at low doses, on dopamine D2/D3 autoreceptors. This atypical profile may explain the therapeutic efficacy of amisulpride in the treatment of both positive and negative symptoms of schizophrenia.

"jasoncrest" you're on the right way !

 

[benzofan]

What I don't understand is : why low dose of Solian (50mg/day) are no more effeciency after 3-4 months of use. And I can ensure you, you can increase the dose (due to an eventual tolerance) it doesn't work at all

If somebody has an exaplanation ? don't hesitate...