The mode of action of sulpiride as an atypical antidepressant agent

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.