REVERSAL OF THE DEPRESSOR ACTION OF N-ISOPROPYLARTERENOL (ISUPREL) BY ERGOTAMINE AND ERGOTOXINE

¹ Pharmacology Section, Sterling-Winthrop Research Institute, Rensselaer, New York

1. The pressor responses to intravenously administeted epinephrine and l-arterenol are potentiated by small doses of ergotamine and ergotoxine. This results largely from an increased cardiac action as indicated by increases in pulse amplitude (Anderson manometer) and increases in the amplitude of ventricular contraction (myocardiograms).

2. The vasodepressor action of Isuprel is reversed to vasopressor action by small doses of ergotamine or ergotoxine. This reversal is associated with a marked increase in the amplitude of ventricular contraction, in pulse pressure and in rate.

3. Cardiac stimulation by 1-(3,4-dihydroxyphenyl)-2-cyclopentylamino-1-butanol and 1-(3,4-dihydroxyphenyl)-2-isopropylamino-1-butanol (WIN 3046) is small. Vasodepressor action of these compounds is seldom reversed by doses of ergotoxine or ergotamine that readily reversed Isuprel.

4. Papaverine, which produces vasodilatation along with cardiac stimulation, may be reversed by ergotization. Therefore, the potentiatiops and reversals described in this communication appear to result from an increase in cardiac output into a vascular bed which has been thrown into a sustained state of vasoconstriction by the reversing drug.

The registered trade marks used in this communication are identified as follows: Gynergen, ergotamine tartrate, Sandoz Chemical Works, Inc.; Prostigmin, neostigmine methylsulfate, Hoffmann-La Roche, Inc.; Pitressin, beta-hypophamine tannate, Parke, Davis and Co.; Pentothal, thiopental sodium, Abbott Laboratories; Isuprel, N-isopropylarterenol, Winthrop-Stearns Inc.