STUDIES ON VERATRUM ALKALOIDS. XLII. THE ACTION OF SOME ESTERS OF PROTOVERINE WITH ACETIC ACID ON MAMMALIAN SKELETAL MUSCLE

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The effects of a series of semisynthetic esters of protoverine with acetic acid on the circulation and on the contraction of the gastrocnemius-soleus muscle were studied in anesthetized cats. Protoverine penta-, tri-and hexaacetate (in this order of potency) caused a marked increase in tension output after a single stimulation (twitch tension) without affecting the magnitude of tetanic tension. The single action potential normally seen after a single stimulus was replaced by a brief series of oscillations. The effect was also observed in chronically denervated muscles. The effect of successive doses was cumulative and the maximal effect lasted for at least 5 hr. The aeetonides of protoverine di- and triacetate were inactive, as was protoverine isopentaacetate. Under chloralose anesthesia the alkaloids active in muscle caused only a mild hypertension which was accentuated by vagotomy and sectioning of the carotid sinus nerves. Under pentobarbital, a hypotensive response to the pentaacetate was usually observed. The protoverine acetates represent a second group of veratrum alkaloids (after the germine acetates) with marked effect of skeletal muscle in doses not causing hypotension.