Neuroleptics sigma receptors

Remoxipride is a selective D2 antagonist with higher affinity for the D2S subtype of receptors. It has no affinity for 5-HT, adrenergic, muscarinic or histamine receptors but, unlike the other atypical neuroleptics, does bind to sigma receptors (see p. 453 for possible importance of sigma receptors). 

Both phencyclidine and ketamine bind with high affinity to a number of receptors in the brain, but it is now accepted that the primary target is the sigma-PCP receptor site located in the ion channel of the NMDA excitatory amino acid receptor complex. The precise function of this receptor in the brain is still the subject of debate. It is now known that there are two distinct sigma receptor sites in the mammalian brain (ctj and a2) which are not associated with the NMDA receptor complex. Haloperidol and the atypical neuroleptic remoxipride bind with high affinity to such sites, and it has been postulated that some typical and atypical neuroleptics may owe some of their pharmacological effects to their action on such receptors. 

Regarding neuroleptic-induced dystonias, it is well known that typical neuroleptics cause catalepsy in rats and movement disorders in man. By contrast, the atypical neuroleptics clozapine and sulpiride have a low propensity to cause movement disorders in man even though they have established antipsychotic effects. These atypical neuroleptics, unlike many of the typical neuroleptics, have a low affinity for sigma receptors which lends support to the hypothesis that the dystonias produced by typical... 

Sigma receptor antagonists for reducing the motor side-effects of neuroleptics Antispasmodics, muscle relaxants Cytotoxic agents (high dose)... 

Vilner, B.J., Bowen, W.D., 1993. Sigma receptor-active neuroleptics are cytotoxic to C6 glioma cells in culture. Eur. J. Pharmacol., Mol. Pharmacol. Sect. 244, 199-201. 

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