Pharmacological classification of benzamides.

Abstract

The problem of classifying benzamides is, in general, the same as classifying neuroleptics. A pharmacological classification of neuroleptics can be established on the basis of the following criteria: specificity of action on dopaminergic receptors; penetration into the CNS; dopaminergic profile in the CNS; relative binding with respect to subclasses of DA; preferential antagonism of certain effects of apomorphine; preferential affinity for dopaminergic structures; activating effects on DA systems at low doses; different clinical effects: antiemetic, psychiatric (antihallucinatory and disinhibitory), neurologic. A relationship between biochemical, behavioural and clinical effects is proposed: antihallucinatory effect: decrease of dopaminergic function; disinhibitory effect: increase of dopaminergic function. We emphasize the problem of doses used because the different effects occurred for a given drug at different doses. This hypothesis suggests that positive symptomatology of schizophrenia is related to hyperdopaminergic activity, negative symptomatology is related to hypodopaminergic activity. Classification of benzamides: metoclopramide: peripheral dopaminolytic activity antiemesis without psychiatric or neuroleptic effects with low doses. sulpiride, tiapride, DAN 2163: peripheral effects + preferential blockade of D3 and D4 receptors, central DA activation with low doses, disinhibitory effects. With high doses, decrease of specificity for subclasses of DA receptors, central DA inhibition, antihallucinatory effects but little extrapyramidal symptomatology and sedation. sultopride: central DA inhibition, antihallucinatory effects, sedative and neurological effects.