Abstract
Respiratory effects of potent hypotensive pure alkaloids and mixtures from the veratrums were determined by measuring their effect upon ventilation volume and by noting the occurrence of short periods of apnea and respiratory arrest. Pure alkaloids included veratridine, germidine, germitrine, neogermitrine, germerine, alkaloid G, alkaloid VB, protoveratrine, veratramine and cevadine. Mixtures tested were an acetic acid-propylene glycol extract of dried ground root of Veratrum viride, Veriloid, veratrine, and PNP 111 . Dosage was determined by hypotensive potency of these agents using multiples of the standard dog assay dose. At the standard assay dose (a close approximation of the clinically desired dose) the respiratory depressant action is fleeting and equivocal. At three times the hypotensive dose, cevacline, veratramine, and veratrine produced respiratory stimulation with an increase in minute expiratory volume. The other agents tested depressed ventilation 40-60 per cent at the three multiple dose, with no statistical differentiation of the degree of depression possible.
The occurrence of periods of apnea and of respiratory arrest suggested a depression of central drive as one mechanism by which decreased minute volume had been produced. Altered respiratory tracings suggested the presence of bronchial constriction.
By the method of electrophrenic stimulation, effect of decreased central drive was eliminated. These experiments suggested that bronchoconstriction accounted for approximately 60 per cent of the observed decrease in minute volume, and that this decrease was independent of vagal factors and of cholinergic effects. It was concluded that the respiratory depression produced by Veratrum derivatives was dependent upon (1) reduction in central drive, and (2) bronchoconstriction due to either direct action of the agents upon the bronchial smooth muscle, or to non-vagal, non-cholinergic reflexes.
Footnotes
- Received October 8, 1951.
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