Posted by Questionmark on April 10, 2006, at 3:12:34
In reply to Re: Amisulpride Sucks So Far.... » linkadge, posted by SLS on April 9, 2006, at 19:50:18
> > I wouldn't think there would be latency either. The rational for this drug strange/mixed. It would not need time to desensitize dopamine autoreceptors like perhaps a MAO-B inhibitor. Wasn't it thought to work as dopamine autoreceptor antgonist ?
> >
> > The other issue is that, it still is an antipsychotic. I think it has strong antagonistic affinity for D3 receptors (which are heavily located in the neucleus accumbens). So the net effect on dopaminergic neurotransmission, I don't know.
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> Me neither.
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> I didn't know about the D3 antagonism. I wonder what would happen if one were to mix amisulpride with either pramipexole or ropinirole. I guess it would depend upon the relative binding affinities of each drug to the pre- and post- synaptic receptors. One would hope that amisulpride would be stronger at the presynaptic D2 and the agonists stronger at the postsynaptic D3.
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> - ScottAccording to the first abstract below, amisulpride supposedly should be primarily antagonistic at D2 & D3 autoreceptors (and therefore enhances dopamine transmission) in the frontal cortex, and it supposedly should have primary agonistic actions at D2 & D3 postsynaptic receptors (and therefore inhibit dopamine transmission) in the limbic system. The specific consequences of these actions-- i'm not sure.
Of course, these pharmacological characteristics might only exist at certain doses. Maybe the opposite occurs at, say, lower doses. It would seem like this should be the case at least in regard to the limbic system effects, since i would suspect "dopamine rush"-like effects to come through DA stimulation in the limbic areas and antipsychotic properties to result from DA inhibition there. But heck, i don't know.
Interesting drug though._Amisulpride: Progress and Outcomes._
Lecrubier Y.
The French Institute of Health and Medical Research.
Hjpital La Salpetriere, Paris, France.
Curr Med Res Opin 2002;18 Suppl 3:s18-22
[Not sure what that journal title is.]ABSTRACT
Amisulpride is a unique atypical antipsychotic that selectively blocks D2 and D3 receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission, and postsynaptically in the limbic areas, possibly reducing it. Thus dopaminergic over-activity in the frontal cortex, and under-activity in the limbic areas, can be treated simultaneously, alleviating both positive and negative symptoms of schizophrenia, respectively. In acute schizophrenia, amisulpride is at least as effective as haloperidol, with a greater number of patients responding to treatment as determined by Clinical Global Impression (CGI scores (p = 0.014). In addition, amisulpride is associated with a lower incidence of extrapyramidal symptoms (EPS) as determined by Simpson-Angus scores (SAS) when compared with haloperidol (p = 0.0053). Amisulpride showed similar efficacy to risperidone as determined by the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Symptom Score (PANSS) positive subscale; a trend towards greater improvement of negative symptoms as determined by PANSS negative subscale compared with risperidone; and similar levels of EPS. Amisulpride uniquely benefits patients with negative symptoms and is the only antipsychotic to demonstrate efficacy in patients with predominantly negative symptoms. Amisulpride maintains its efficacy when used for medium/long-term treatment as demonstrated in studies of up to 12 months. Amisulpride demonstrates greater improvement in controlling symptoms compared to haloperidol. In terms of the relevance of the effects, a superiority is observed for quality of life, social adaptation and functioning as measured by the Quality of Life Scale (QLS), Clinical Glocal Impression scale (CGI) and Functional Status Questionnaire (FSQ) scales. Amisulpride also has one of the lowest potentials of all the antipsychotic agents for weight gain. The clinical evidence for amisulpride supports its earlier pre-clinical potential, showing it to be an atypical antipsychotic agent with specific clinical advantages.
__A Review of the Pharmacokinetics, Tolerability and Pharmacodynamics of Amisulpride in Healthy Volunteers.__
Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G.
Department of Internal Medicine-Clinical Development.
Sanofi-Synthelabo, Chilly-Mazarin, France.
Human Psychopharmacology, 2002, Jan, 17(1):1-13.ABSTRACT
Amisulpride binds selectively to dopamine D(2) and D(3) receptors in the limbic system. Low doses of amisulpride preferentially block presynaptic D(2)/D(3)-dopamine autoreceptors, thereby enhancing dopaminergic transmission, whereas higher doses block postsynaptic receptors, thus inhibiting dopaminergic hyperactivity. Amisulpride is clinically effective on the negative symptoms of acute schizophrenia exacerbations at low dosages (50-300 mg/day), and also on the positive symptoms of the disease at high dosages (400-800 mg/day). Nineteen clinical studies involving 358 volunteers have investigated the pharmacokinetics, pharmacodynamics and tolerability of amisulpride. Amisulpride shows linear pharmacokinetics, a bioavailability of 48%, low protein binding (17%) and an elimination half-life of approximately 12 h. It is predominantly eliminated in the urine as the parent compound. It exhibits no significant detrimental effects in psychometric or memory tests up to the dose of 400 mg/day, inducing only mild impairment at high doses, whereas EEG data suggest an alertness-enhancing effect at low doses (/= 50 mg). Moreover, amisulpride does not potentiate the depressant effects on the central nervous system of alcohol and lorazepam. This tolerability profile is clearly better than that of haloperidol 4 mg/day and is consistent with a weak blocking effect on striatal D(2) receptors. In summary, studies in humans have shown that amisulpride is free of behavioural toxicity at doses exerting clear antipsychotic efficacy and confirm that its CNS effects may vary with the dose administered.
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