ON THE PHARMACOLOGY OF MYANESIN, WITH PARTICULAR REFERENCE TO ITS INTRAMUSCULAR ADMINISTRATION

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Abstract
The authors studied the pharmacological properties of myanesin, particularly with reference to finding a safer method of admn. Myanesin was admd. to 18 dogs intraven. in doses ranging from 10-200 mg./kg.; 15-25 mg./kg. produced appreciable ataxia, about 50 mg./kg. produced actual paralysis, and about 200 mg./kg. produced fatal respiratory paralysis. Myanesin was also administered to 10 dogs intramusc. in doses ranging from 25 to 150 mg./kg. No loss of righting reflex was noted. Transient ataxia was seen with doses of 50 mg./kg. or more. Respiration was not appreciably affected with the above doses. Myanesin is rapidly absorbed after intramusc. admn. Approx. twice the intraven. doses must be given intramusc. to yield equivalent plasma levels. About 2 mg./lOO cc. of plasma is the minimal level necessary to produce ataxia and muscular relaxation. The hemolytic effect of myanesin was studied on dogs; 9 received the drug intraven. and 9 intramusc. Various solvents and various concns. of myanesin in these solvents were tested for hemolytic action by a modification of the standard procedure for determining the icterus index. Intraven. myanesin in greater than 1% concns. in all vehicles tested produced considerable hemolysis. Myanesin can be admd. intraven. only in a 1%. soln. without destroying red blood cells. Intramusc. myanesin in doses up to 25 mg./kg., dissolved in 40% propylene glycol, or up to 50 mg./kg. or more, dissolved in a vehicle of 10% urea and 8% propylene glycol, did not produce any detectable hemolysis. Intraven. anesthesia was produced in 3 groups of 4 dogs, each receiving surital (Na 5-allyl-5-(methylbutyl)-2-thiobarbiturate) or thioethamyl (Na 5-ethyl-5-isoamyl-2-thiobarbiturate) with or without myanesin. Addition of myanesin to surital produced an instantaneous induction. Myanesin added to thioethamyl produced anesthesia lasting twice as long as when thioethamyl was used alone. Expts. on 24 mice showed myanesin to be detoxified by the liver. Intra-perit. injns. of myanesin and benzimidazole in 119 mice showed the PD50 potency of each to be identical; combined equivalent doses of each gave a purely additive cerebrospinal depressant effect.
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