THE CARDIOVASCULAR AND RESPIRATORY EFFECTS OF 3-HYDROXY-2-PHENYL CINCHONINIC ACID

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

The rapid intravenous injection of 5 mgm./kgm. or more of HPC into unanesthetized and anesthetized dogs produced the typical Bezold effect—respiratory depression or apnea associated with hypotension and bradycardia. Tachyphylaxis was readily demonstrated, in that animals became immediately refractory to subsequent doses of HPC and remained so for periods of at least eight hours. However, germitrine (a veratrum alkaloid), phenindamine (Thephorin) and Nu 1525 still elicited the Bezold effect in animals refractory to HPC. Thus, it appears that HPC and germitrine (and phenindamine) may act on different sensory receptor areas. The cardiovascular and respiratory effects of HPC have been shown to he reflex in origin. The sensory impulses of the respiratory effect and both the sensory and motor impulses of the cardiodecelerator effect are carried in the vagus. Vagotomy abolished all reflex effects of HPC, germitrine, phenindamine, and Nu 1525 while doses of 2 mgm./kgm. of atropine abolished only the cardiovascular reflex effects of these agents. The phenomenon of tachyphylaxis with HPC is explained on the basis of a prolonged blockade of the sensory receptors of both the respiratory and cardiovascular effects by the compound.