Absence of opiate and histamine H2 receptor-mediated effects of clonidine

The possibility that clonidine might exert some of its effects via opiate or histamine H2 receptors has been suggested from observations in animals and man. We undertook a double-blind, randomized study in six normal subjects, comparing the effects of 0.2 mg intravenous clonidine after pretreatment with 300 mg cimetidine, 0.8 mg naloxone, and saline. There was no attenuation of the hypotension, bradycardia, sedation, inhibition of salivary flow, or reduction in plasma catecholamines after cimetidine and naloxone, but the fall in plasma catecholamines ater clonidine correlated with blood pressure, sedation, and salivary flow, suggesting a central adrenergic mechanism for these effects. It is not known whether cimetidine can cross the blood-brain barrier after short-term dosing. We conclude that in normotensive subjects the short-term effects of intravenous clonidine are probably not mediated by an action at peripheral histamine H2 or central opiate receptors.