ACTION OF OCTOPAMINE AGONISTS AND STEREO ISOMERS AT A SPECIFIC OCTOPAMINE RECEPTOR

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Abstract
SUMMARY: 1. (±)‐Octopamine, (±)‐N‐methyl octopamine and (‐)‐α‐methyl octopamine increase the amplitude of contraction of the spontaneously beating ventricle of the mollusc Tapes watlingi through action on a specific octopamine receptor.2. Unlike the excitatory responses to dopamine, noradrenaline or serotonin, the excitatory response of the ventricle to agonists at the octopamine receptor is attenuated by metoclopramide.3. Compounds with potent agonist activity at the octopamine receptor all have a single phenolic hydroxyl in the para position of the benzene ring and a β‐hydroxyl group in the phenethylamine side chain. O‐Methylation of the para phenolic group or removal of the /3‐hydroxyl group results in complete loss of agonist activity. Bulky substituents but not a single methyl group on the amino groups impair agonist activity.4. The octopamine receptor is stereo‐selective, (‐)‐octopamine is more than twenty times more active than (+)‐octopamine.5. The weak octopamine‐like activity of (‐)‐N‐methyl and a‐methyl meta octopamine indicates that the stereo‐selective receptor has a relative rather than an absolute requirement for a single phenolic hydroxyl in the para position of the benzene ring.6. These data indicate the presence of a specific, stereo‐selective receptor for octopamine in the ventricle of the mollusc Tapes watlingi.7. The stereo‐selectivity and structural specificity of the octopamine receptor differentiates it from receptors for dopamine and serotonin also present in the ventricle.