STUDIES OF THE ACTIONS OF METHYL-ADRENALIN; METHADREN

¹ Department of Physiology, University of Wisconsin Medical School, Madison

In the nembutalized rabbit 25 to 30 times as much methadren as adrenalin injected intravenously gave comparable pressor effects. In the dog a higher ratio of 30 to 50 times as much methadren was required, both in the unanesthetized spinal animal and those under surgical cyclopropane, ether, or vinethene anesthesia.

In the dog under ether there were no cardiac irregularities and under cyclopropane and chloroform fewer irregularities than in the control experiments with pressor dosage of 0.50 mgm. per kilogram of methadren (comparable to the standard test adrenalin dosage previously studied). Thus cyclopropane does not enhance the activity of this tertiary amine on the automatic tissue of the dog's heart as has been shown previously to occur with adrenalin or other primary or secondary sympathomimetic amines having the catechol nucleus.

Both in the isolated perfused guinea pig lung and the intact anesthetized dog, bronchiolar spasms from histamine could be relieved by a pressor dosage of methadren comparable to adrenalin.

Twenty-five to forty times as much methadren as adrenalin in 1 or 2 per cent procaine gave equivalent prolongation of local anesthesia of the rabbit's eye.

Intravenous methadren in the dog gave less pronounced and less prolonged glycogenolytic response than the comparable pressor adrenalin dosage. Subcutaneous injection in the rabbit gave a comparable rise of blood sugar but of shorter duration.

For rats the MLD₅₀ for methadren per kilogram has been found to be subcutaneously 105 mgm., intraperitoneally 50 mgm., and intravenously 5 to 6 mgm.

For rabbits the figures are 25 to 30 mgm., 20 to 25 mgm., and 2.50 to 3.75 mgm. respectively.

In puppies the intravenous toxicity has been found to be between 10 to 15 mgm. per kilogram and in adult dogs 7.5 mgm. per kilogram.