Hi my colleague clinical pharmacist,

it is not easy question however i will try to answer as well is possible:

Sulpiride is considered as atypical antipsychotic, because its specific mode of action compare to 'typical antipsychotics'. Usually 'typical' antipsychotics have strong actions (potency) towards D2 receptors, although not only in the limbic system, which is primary site of action. Because of their activity towards D1, D3, D4 and D5 receptors there is possible to observe several important adverse events (dyskinesia tardive, prolactine levels, tremor ...).

Sulpiride has dose dependent action on D2 receptors and in low (small) doses its actions is primarily via D2 autoreceptors and in high doses as antagonist on D2 receptors and small action on D1 receptors. Because of this mode of avtions in small doses we can use sulpiride as antidepressants and in higher doses as antipsychotic drug (potency towards D2 heteroreceptors is higher than autoreceptors). This is very specific mode (mechanism) of action and consequently we have specific so called 'dose-dependent' action.

The Second exemption of sulpiride is its action via D3 receptors. Because of this activity (potency and efficacy) on D3 receptors there is very few possibility of serious adverse events in form of dyskinesia tardive and tremor in compare to haloperidol. Its D3 activity and small D1 activity (high doses) is key mode of action in ensuring the safety pharmacotherapy.

The third important feature of sulpiride is connected with agonism/antagonism. Often named as partial agonist sulpiride has similarities than partial agonists. In the case of low concentration acts on presynaptic autoreceptors. In the case of many combinations of antipsychotics there is a place for sulpiride. With its special activity there are some positive trials where the antipsychotic polypharmacy has been used and proven. Especially interesting is its combination with clozapine, however there is special caution required, because of possible prolongation with QTc.

The fourth important thing is its use for negative symptoms of schizophrenia, for which sulpiride is better than 'typical' antipsychotics.

Taken together there are many features, which are connected with atypical antipsychotic and therefore it is more atypical antipsychotic than typical, although potency towards D2 receptors is very high compared to atypical antipsychotics.

If i conclude, this is very interesting agent for pharmacologists and psychiatrists and according to the trials, where polypharmacy was tasted, supiride/amisulpiride is underprescribed. In real clinical practice there is high prevalence of haloperidol and risperidone use in combinations with other antipsychotics, although we do not have evidence to do it. On the another hand, there are positive trials of sulpiride/amisulpiride use especially with clozapine and olanzapine. As clinical pharmacist specialist within psychiatry i often suggest to add the sulpiride or combine, when antipsychotic polypharmacy is under question.

Regards,

Matej

Thank you Matej,

That was a very comprehensive answer!

sulpride is an atypical antipsychotic drug; of the benzamide class used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder but its side effects (Extrapyramidal side effects) proven its blockade action on D2 central receptors also

Amusulpiride has been introduced under the name of Dan long time before one would distinguish typical from  atypical neuroleptics i. e. the late eigthies

Sulpiride is considered as an atypical anti-psychotic, for the reasons mentioned below:

"It can be said that sulpiride exerts a disinhibitory effect in both depression and schizophrenia but this is not associated with mechanisms through which typical antidepressant or anxiolytic agents act. Sulpiride acts selectively as a dopamine receptor antagonist in the brain, its effects on other neuronal systems being extremely limited. Indeed, it may act even selectively within the dopamine systems in that it would appear it specifically interacts with one sub-population of cerebral dopamine receptors. Within a given dopamine receptor system sulpiride may exert a differential pre-synaptic action on dopamine neurones although the evidence for this remains controversial. The disinhibitory effects in depression may be due to a preferential pre-synaptic action of the drug on dopamine neurones causing over-activation of cerebral dopamine post-synaptic receptors causing behavioural arousal and motor facilitation. On the other hand, the disinhibitory effect of sulpiride in schizophrenia may also involve the preferential pre-synaptic action of the drug coupled with the specificity of post-synaptic action to result in little sedation or motor retardation. Sulpiride may also differentially antagonise post-synaptic dopamine receptors in different brain areas and this may also be critically involves in its unusual spectrum of neuroleptic action.

Hope this explanation may help you better.

Levosulpiride is currently used more as a prokinetic agent along with rabeprazole for GERD

These comprehensive answers illustrate that the dichotomy between so-called "typical" and "atypical" drugs is not a helpful one, since it is based on supposed differences in the risks of extrapyramidal adverse effects, which are (a) not homogeneous from drug to drug within the supposed two types and (b) not constant from person to person. It would be better to abandon the terminology and instead, for each drug, describe the pharmacology and the risks of adverse drug reactions.

In the antipsychotic history, only first gen of antipsychotic eg Chlorpromazine are ''typical'', so sulpiride is an atypical psychotic.

I agree with many answers above. Actually many people dont consider sulpiride an atypical antipsychotic because it appeared in the market many years before risperidone. Paradoxically amisulpiride is considered an atypical antypsichotic ( and it'is much more expensive ).

My own opinion is that the vast majority of pharmacologists and psychiatrists would consider sulpiride to be an atypical antipsychotic.

Dr. Stuhec and Dr. Aronson summarized the issue very well; typical antipsychotics appear to be defined primarily by:

• D2 binding characteristics.
• Their propensity to cause extrapyramidal side because of this.

I would add that 5-HT2A binding (antagonism) of seemingly all modern atypicals is also often cited as significant to their novelty, though I think Thorazine has this action, as well.

Unfortunately, I have found that the literature establishing sulpiride's unique D2 autoreceptor activity is relatively sparse and now quite dated. Regrettably, it seems quite common in psychopharmacology that a small number of studies forever define the profile of a drug, leading to overconfidence as to its mode of action, especially in basic research.

I would also add that structure is surprisingly important: practically all commonly cited typicals are either butyrophenone (haloperidol) or phenothiazine (chlorpromazine) derivatives.

Atypicals are almost all either tricyclic derivatives (e.g., olanzapine), or resemble risperidone (benzisoxazole-like) or aripiprazole (phenylpiperazines). This distinction appears arbitrary but does tend to predict binding profiles.

Sulpiride is a benzamide, so it not being a butyrophenone or phenothiazine already makes it less 'typical' in this sense. Though trivial, I think these structural considerations do actually impact real-world categorization.

Classically, the distinction between an atypical and a typical antipsychotic comes from its ability to block 5-HT receptors, leading to fewer extrapyramidal side effects.

Amisulpride doesn't show activity at 5-HT receptors, but only at D2 and D3 receptors. At a low dose, amisulpride binds selectively to presynaptic autoreceptors, increasing the DA transmission in the meso-cortical region and improving negative symptoms. At a high dose, amisulpride blocks postsynaptic D2 receptors in the limbic system, decreasing DA transmission and improving positive symptoms.

The fact that it is considered an atypical antipsychotic probably comes from its unsual mechanism of action, its ability to treat both positive and negative symptoms and its relatively favorable side-effect profile (propensity to extrapyramidal side effects comparable to atypical antipsychotic). As such, it could be considered as an ''atypical-atypical''.

I agree with Jeffrey K Aronson; I think the terms atypical and typical should be abandonned when talking about antipsychotics.