THE REFLEX RESPIRATORY AND CIRCULATORY ACTIONS OF SOME CINCHONINIC ACID DERIVATIVES AND A NUMBER OF UNRELATED COMPOUNDS

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

1. 3-Hydroxy-2-phenyl cinchoninic acid (HPC) and a number of derivatives produce Bezold-like reflex effects (apnea, fall of blood pressure and bradycardia) when injected intravenously into dogs. A hydroxyl group in the 3-position was found to be essenstial for this activity. The most potent derivative in the series was 3-hydroxy-2-phenyl-8-carboxy cinchoninic acid.

2. Since no correlations could be demonstrated between the reflex effects and the antidiuretic activity of a series of cinchoninic acid derivatives, it was concluded that the reflex circulatory effect played only a minor role in the antidiuretic actions.

3. Except for the 3-hydroxy derivative (HCA), all cinchoninic acid derivatives which possessed reflex activity also exhibited the phenomenon of tachyphylaxis in dogs. Durations of refractory period for HPC arid the 8-carboxy derivative was 8 and 1.5 hours, respectively.

4. HPC produced essentially similar reflex effects in the dog and the cat in the same dosage. However, tachyphylaxis was absent in the cat.

5. Other species differences in reflex activity of several compounds were demonstrated. Phenyldiguanide and 2--naphthylethylisothiourea possess potent Bezold-like reflex activity in the cat and rabbit but not in the dog.

6. Phenindamine and two closely related derivatives possess varying intensities of reflex activity in the dog and cat but no correlations between antihistamine and reflex activity was observed.