THE ACTIONS OF BARBITURATES ON THE CONTRACTIONS OF VOLUNTARY MUSCLE

¹ Department of Pharmacology, Jefferson Medical College, Philadelphia, Pa.

Four types of effects on voluntary muscle function have been shown to be evoked by relatively low concentrations of the barbiturates, the incidence and intensity of the effect varying with the barbiturate and with the test object:

1. Potentiation of the maximal twitch by a probable direct action on the fiber. The thiobarbiturates are more active in this respect and the relative potency of the barbiturate series parallels their pharmacologic potency generally and their protein-binding affinity.

2. A curare-like activity which is demonstrable in augmentation of the action of curare on artificially stimulated fast muscle. The oxybarbiturates regularly manifest this property and the magnitude of this effect tends to be correlated again with pharmacologic potency. The thiobarbiturates reveal the curare-additive tendency only under special conditions.

3. A type of anti-curare activity, characteristic only of the thiobarbiturates, in which partial tubocurarine paralysis of the artificially stimulated tibial is reversed. A lack of specificity is suggested by the activity of thiopental in reversing as well the actions of depolarizing drugs such as decamethonium, acetylcholine and neostigmine.

4. A protective action against curare, demonstrated as yet only on naturally activated muscles of the neck and chest. This property is manifested only by certain barbiturates, dissociated from their activity otherwise, with the greatest potency in the present series resting on a 1-methylbutyl group as the R² substituent.

The barbiturates, although varying considerably in their ability to increase twitch tensions, appear able to penetrate muscle and produce their effects in periods of time that do not differ markedly.