PT  - JOURNAL ARTICLE
AU  - R. P. WALTON
AU  - C. B. PREACHER
AU  - W. M. CANNON
TI  - ACUTE AND CHRONIC TOXICITY OF AN ALIPHATIC AMINE, METHYLAMINO-ISO-OCTENE (Octin)
DP  - 1948 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 214--225
VI  - 92
IP  - 3
4099  - http://jpet.aspetjournals.org/content/92/3/214.short
4100  - http://jpet.aspetjournals.org/content/92/3/214.full
SO  - J Pharmacol Exp Ther1948 Mar 01; 92
AB  - (Dosages in the following represent the dose per kg. of body weight.) 1. Methylamino-iso-octene hydrochloride administered intravenously was found to have an LD50 of 17.5 mg. (S.E. 2.7) in mice, of 17.6 mg.(S.E. 1.0) in rabbits and of 25.8 mg. (S.E. 2.0) in dogs. Administered subcutaneously, the estimated LD50 was 171 mg. (S.E. 9.5) in mice, 101 mg. (S.E. 8.9) in rabbits and 76.3 (S.E. 9.1) in dogs. Administered orally to dogs the mucate salt was found to have an estimated LD50 of 148 mg. (S.E. 55). 2. The acute manifestations in dogs, resembled, in several particulars, those of cocaine excitation; characteristic manifestations in rabbits and mice were less conspicuous. 3. On the isolated rabbit heart, the most consistent effect was a temporary depression. Circulatory effects in the open chest dog preparation are primarily depressant in the dose range of 20 to 40 mg.intravenously. In the dose range of 0.5 to 10mg. intravenously effects are biphasic (depressor-pressor) with respect to blood pressure; they are similarly biphasic with respect to contractile force of the heart after repetition of the smaller doses in this range or with the first of the higher doses in this range. Initial intramuscular doses of 15 mg. per kg. produce only stimulation of rate and contractile force with an increase in blood pressure. 4. Prolonged administration of octin hydrochloride to roosters in daily doses of 20 mg. intramuscularly failed to produce gangrene of the comb, while ergotamine tartrate readily produced gangrene of the comb tips with other roosters from the same brood. 5. On chronic administration, no significant effects were observed in mice receiving octin mucate in average daily doses of 40 mg. orally for periods up to 195 days (total 7.6 gm.), in dogs receiving the mucate at an approximately similar rate for periods up to 316 days (total 13.2gm.), and in dogs receiving daily doses of 4 mg. of the hydrochloride intramuscularly for periods up to 127 days (total 900 mg.). 1948 by The American Society for Pharmacology and Experimental Therapeutics