amisulpride came into the indian market a few years back with hypes and hopes in the management of schizophrenia .
its broad spectrum effectiveness with lower chances of extrapyramidal symptoms ( eps ) and metabolic syndrome did help psychiatrists to treat schizophrenia and related disorders more effectively .
although this antipsychotic does not block serotonin receptors at all , it is a high - affinity and highly selective d3/d2 receptor antagonist with atypical properties .
its selective affinity for dopamine receptors in the limbic structures , but not in the striatum , leads to a low risk of extrapyramidal side effects .
all available reports suggest that chance of eps is very less with amisulpride at doses < 400 mg / day .
however , there are sporadic reports of drug - induced eps including dystonia and akathisia even in patients receiving low doses of amisulpride . here
a 30-year - old male with schizophrenia for the past 10 years now presented with predominantly negative symptoms .
he was on olanzapine 15 mg / day for more than 6 months without much improvement .
hence , amisulpride was instituted with a starting dose of 50 mg / day with a gradual increment up to 300 mg / day within 14 days .
the patient came after 14 days to the casualty with features of parkinsonian syndrome such as slowed gait , mild rigidity , salivation , and bradykinesia .
he was hospitalized , amisulpride was immediately stopped , and trihexyphenidyl 4 mg / day was given to manage the side effect .
his eps gradually subsided and for negative symptoms , clozapine was introduced at a small dose of 25 mg / day and gradually increased to 200 mg / day over a period of 10 days . at the time of discharge , on the 14 day , he was free from parkinsonian symptoms .
subsequent follow - up showed no parkinsonian symptoms and he had modest improvement in negative symptoms . a 48-year - old male with schizophrenia for the last 20 years
was treated with various antipsychotics without much improvement . since the last 6 months , he was on olanzapine 15 mg / day .
as there was no significant improvement , his olanzapine dose was gradually tapered and stopped over a period of 14 days and was started on amisulpride 100 mg / day and was increased to 200 mg / day over a period of 3 weeks .
the patient returned on the 24 day with severe parkinsonian symptoms . in this patient also , there was no prior history of parkinsonism .
we managed him with injection promethazine 25 mg intramuscular bid first 3 days along with trihexyphenidyl 2 mg bid after stopping amisulpride .
after 7 days , parkinsonian symptoms improved considerably and clozapine was introduced at a dose of 25 mg / day which was subsequently increased to 100 mg / day on the 10 day and the patient was discharged .
since the discovery that clozapine induces fewer eps and is more effective for negative symptoms than conventional antipsychotics for the treatment of schizophrenia , psychopharmacological research has focused on the development of drugs that block central 5-ht2 receptors more than d2 receptors .
combined 5-ht2/d2 receptor antagonism is the most current explanation for the so - called  atypical  profile of some antipsychotics .
amisulpride at low doses binds selectively to dopamine d2 , d3 autoreceptors , thereby enhancing dopaminergic transmission and thus might be effective for negative symptoms .
it has no affinity for d1 , d4 , and d5 receptor subtypes . at higher doses
, it blocks postsynaptic receptors , thus inhibiting dopaminergic hyperactivity . at the same time , amisulpride has greater specificity for the limbic system and thus has low incidence of eps .
amisulpride binds more loosely than dopamine to the dopamine d2 receptor and is rapidly dissociated from the dopamine d2 receptor .
low - dose therapy with amisulpride is associated with a significantly lower blockade of striatal dopamine d2 receptors than is seen during high - dose treatment . however , a significant striatal d2 blockade was demonstrated at therapeutically effective dose ranges , and a good relationship between the degree of striatal dopamine d2 receptor occupancy and the amisulpride plasma concentration or the administered dose was shown . in general , asians are slow metabolizers .
low body weight and slow metabolism may increase the plasma concentration of drugs causing side effects .
reported a low postsynaptic d2 occupancy in the striatum at low doses of amisulpride ( 50100 mg / day ) .
it has also been suggested that extrastriatal binding could mediate the effect on negative symptoms .
the probable causes of eps with low doses of amisulpride could be that it blocks postsynaptic d2 receptors significantly in striatum without much effect in the mesolimbic pathway .
, the lower incidence of eps which is claimed by western researchers as well as pharmaceutical companies should be studied well in the indian context .
we should at least keep this side effect in our minds while starting or increasing the doses .
 amisulpride , recently introduced atypical antipsychotic , is well - known for its broad spectrum effectiveness and lower profile for extrapyramidal side effects ( eps ) . 
 its selective affinity for dopamine receptors in the limbic structures , but not in the striatum , leads to a low risk of extrapyramidal side effects . here 
 , we report two cases of eps associated with lower dose of amisulpride . 
 the proposed mechanism for its causation is also discussed . 
 authors invite more studies , specifically from the indian context to find out the incidence of eps and other associated side effects . 