STUDIES ON VERATRUM ALKALOIDS. XXXIII. THE ACTION OF SOME ESTERS OF GERMINE WITH ACETIC ACID ON THE SARTORIUS MUSCLE OF THE FROG

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

The effect of germine and several of its acetic acid esters upon the sartorius muscle of the frog has been examined. Tension development after a single shock and during tetanic stimulation, rate of tension rise, and duration of contraction were measured. Transmembrane potentials were recorded with microelectrodes.

None of the alkaloids altered the magnitude of tetanic tension in concentrations which caused maximal changes in the response to a single stimulation. Germine, germine monoacetate (GMA), and germine diacetate (GDA), increased twitch tension with only moderate prolongation. Under optimal conditions twitch tension under GMA and GDA was equal to tetanic tension. Germine tetraacetate (GTA), germine isotetraacetate, and germine pentaacetate (GPA) caused an aftercontraction similar to that seen after veratridine. The tension during the aftercontraction never reached the magnitude of tetanic tension.

All alkaloids induced the appearance of repetitive electrical activity in response to a single stimulation. Germine elicited only 2 to 3 afterpotentials; GMA and GDA caused a period of repetitive firing of 130 to 200 milliseconds; after GTA and GPA the period of repetitive firing was between 350 to 900 milliseconds. In all instances the duration and the frequency of the repetitive activity were sufficient to account for the tension development observed. With GMA and GDA the activation of the muscle during the period of repetitive activity was complete, i.e., all fibers participated in the effect of the drug along their whole length. With GTA, GPA and veratridine not all fibers were simultaneously active during the aftercontraction. It is likely that this is due to the critical drug concentration required and to the presence of fatigue in part of the fibers.