DIFFERENTIAL BLOCKADE OF OCTOPAMINE AND DOPAMINE RECEPTORS BY ANALOGS OF CLOZAPINE AND METOCLOPRAMIDE

1. Sulpiride, but not procainamide, antagonizes the excitatory effects of (±)‐octopamine receptors in the Tapes ventricle. Neither compound attenuates dopamine excitation. 2. Clozapine will attenuate the effects of (±)‐octopamine and (‐)‐α‐methyl octopamine at the octopamine receptor but not the excitatory effects of dopamine at dopamine receptors. 3. Clozapine is more potent than its 2‐positional isomer HF 2046 in attenuating octopamine excitation. However, HF 2046, unlike clozapine, will attenuate the excitatory effects of dopamine. 4. These data indicate that replacement of the 8‐chloro substituent in the clozapine nucleus with a 2‐chloro substituent decreases the ability of the compound to blockade octopamine receptors. However, the 2‐chloro‐substituted compound (HF 2046) now has the added ability to blockade excitatory dopamine receptors. 5. The greater potency of clozapine than HF 2046 as an octopamine antagonist suggests that it is the 8‐chloro‐substituted aromatic ring of clozapine which overlaps the aromatic site usually occupied by the octopamine aromatic ring. Copyright © 1978, Wiley Blackwell. All rights reserved