Sympathomimetic drugs: evaluation for acute central hypotensive activity in alpha-chloralose-anesthetized dogs and cats intravertebral artery administration,

dl-Amphetamine, phentermine and their para-chloro derivatives were tested for acute central hypotensive activity after intra-vertebral artery (iva) infusions in alpha-chloralose-anesthetized cats and intact and carotid sinus denervated dogs. Iva clonidine (reference standard) caused immediate reductions in blood pressure and heart rate and carotid sinus denervation (CSD) enhanced the clonidine response. dl-Amphetamine and phentermine did not cause acute hypotensive responses in the dog or cat whereas their para-chloro derivatives did. The vasodepressor response to para-chloramphetamine was inconsistent and transient and not modified by CSD. The magnitude and duration of the chlorphentermine vasodepressor response was minimal in the intact and CSD dog compared to clonidine. In contrast, chlorphentermine in the cat (140-300 mug/kg) caused an acute hypotensive response comparable in magnitude to clonidine (0.6-1.0 mug/kg). The bradycardias observed after iva chlorphentermine were much less pronounced than those associated with iva clonidine at comparable vasodepressor doses. By the i.v. route, each drug caused only pressor responses in the dog and cat. Suppression of the pressor response (resulting from "spill-over" of these alpha-stimulants into the systemic circulation after iva dosing) in the dog with small doses of i.v. phenoxybenzamine did not unmask or enhance the vasodepressor or bradycardic actions to iva administration of drugs. Methysergide prevented the hypotensive response to chlorphentermine in the cat and partially suppressed the response to clonidine; the reverse was true after piperoxan. Lilly 110140 and para-chlorophenylalanine reduced or abolished the effects of iva chlorphentermine. In summary, (1) iva chlorphentermine and clonidine were the only alpha-sympathomimetics tested which were effective as hypotensive substances; (2) the cat was considerably more responsive to iva chlorphentermine than the intact or CSD dog; (3) iva clonidine was more bradycardic than iva chlorphentermine; and (4) both adrenergic and serotonergic components appear to be among the mechanisms involved in the acute iva hypotensive response to chlorphentermine in the cat.