ANTAGONISM OF LOBELINE BY GANGLION-BLOCKING AGENTS AT AFFERENT NERVE ENDINGS

¹ Department of Pharmacology, UCLA Center for Health Sciences, Los Angeles, California

The nature of the antagonism between lobeline and various ganglion-blocking agents at the afferent nerve endings found in the region of the pulmonary artery bifurcation has been investigated in the anesthetized cat. Since stimulation of these endings leads to reflex hypotension, this effect was used to quantify the intensity of afferent stimulation. As neither lobeline nor ganglion- blocking agents act specifically at sensory endings, the experiment was designed to limit the doses of these agents to those that had a significant effect only on the afferent terminals. Tetraethylammonium (TEA) caused a parallel shift of the lobeline dose-response curve to the right without changing the magnitude of the maximum response. The isobol relating the infusion rate of TEA and the response to the intravenous injection of lobeline was linear. Similar effects were observed with hexamethonium and mecamylamine, except that the small range of dosage of antagonist that could be employed precluded isobol determinations with these drugs. These ganglion-blocking agents may be described as competitive or surmountable antagonists of lobeine. Chlorisondamine shifted the doseresponse curve for lobeine to the right, but not in parallel, and reduced the maximum response, suggesting a noncompetitive or unsurmountable antagonism by this agent.