THE REFLEX RESPIRATORY AND CIRCULATORY ACTIVITY OF 1-PYRIDINDENE DERIVATIVES

¹ Department of Pharmacology, Emory University School of Medicine, Emory University, Georgia

The intravenous injection of a number of pyridindene derivatives, including the antihistamine agent, phenindamine, produces a unique reflex response consisting of apnea, bradycardia and hypotension. Increasing the degree of saturation of the pyridindene nucleus from the dihydro- to the hexahydro-derivative produced a 20-fold increase in reflex activity, while the replacement of the 2-methyl by the 2-ethyl group produced a corresponding 4- to 8-fold increase. The activity of the isopropyl analogues was between that of the corresponding methyl and ethyl derivatives. The most active of the ten pyridindene derivatives, 2-ethyl-9-phenyl-2,3,4,4a,9,9a-hexahydro-1-pyridindene (Ro 2-2263), was effective in doses of 62 to 125 microgm./kgm. No correlation between reflex and antihistamine activity was observed.