ACTION OF LOBELINE ON INTRATHORACIC RECEPTORS: A COMPARISON WITH PHENYLDIGUANIDE, SEROTONIN AND VERATRIDINE

¹ Department of Pharmacology, University of California Medical Center, Los Angeles, California

Small amounts of lobeline sulfate (15 µg/kg) given intravenously to a cat anesthetized with -chloralose cause hypotension, bradycardia and apnea due to a pharmacological stimulation of sensory receptors within the thorax. Cardiovascular and respiratory effects are obtained when the drug is injected into the pulmonary vascular bed, but only cardiovascular effects are elicited from the coronary vascular bed. In over half the experimental animals, on injection of the median effective dose of lobeline, the degree of hypotension was greater than the hypertension that subsequently occurred due to stimulation of the carotid and aortic chemoreceptors. The magnitude of the hypotensive response is related to the level of the arterial pressure and is greatly diminished under barbiturate anesthesia.

The characteristics of this early response triad elicited by lobeline are contrasted with those of the responses obtained with phenyldiguanide, serotonin and veratridine which are superficially similar. On the injection of just maximal doses of these drugs into the right atria of cats, lobeline is seen to act consistently 1 second earlier than phenyldiguanide and serotonin. When injected into the left ventricle, the latent period between injection and response is the same. The response to diguanide and serotonin but not that to lobeline and veratridine is blocked by 2-naphthyl-guanidine. The response to lobeline alone is blocked by tetraethylammonium and pentobarbital. Whereas phenyldiguanide has little activity in the dog, lobeline is equi-potent in the dog and cat.

It is proposed that lobeline in small doses stimulates sensory receptors in the pulmonary circulation that are pharmacologically and possibly anatomically distinct from those for the amidines and veratridine. It also stimulates receptors that are pharmacologically distinct from those for the amidines and veratridine in the coronary circulation.