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Taché Y, Taché J, Mécs I, Du Ruisseau P, Selye H.
“Regulation of Resistance to Various Toxicants by PCN (Pregnenolone-16a-Carbonitrile) and Thyroxine”.
J.Med.. 1976;7(6):471-79.
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Abstract
Antagonism between L-thyroxine (T, BDH) and (3beta-hydroxy-20-o-5-pregnene-16-alpha-carbonitrile) (PCN, Upjohn) in protection against drug toxicity was studied. Methods Female Charles River rats (90-110 g) were given 1 or 10 mg PCN b.i.d. by stomach tubeor s.c. T at 50 or 200 mcg once daily, 3 days before giving toxicants, and were continued throughout the observation. Toxicants (per 100 g) given on the 4th day were: (1) Antazoline (A, Ciba) i.p. at 7.5 mg and also at 10 mg on the 5th day. Tremors were assessed at 1 hr and mortality on the 6th day. (2) Carbamazepine (CZ, Ciba) i.p. 20 mg. Sleeping time was determined immediately, mortality at 24 hr. (3) Cocaine HCl (C, Mallinckrodt) i.p. 6 mg. Prostration was measured at 30 min. mortality at 24 hr. (4) Guanethidine (G. Ciba) i.p. 31 mg and measurements as per (3). (5) Ibuprofen (I, Boots) s.c. 40 mg/day from the 4th 11 th day. Intestinal ulcers were appraised at death and mortality listed on 12th day. (6) Ketamine HCl (K, Parke-Davis) i.p. 13 mg and measurements as per (1). (7) LSD (Sandoz) i.p. 300 mcg. Severity of convulsions were measured at 30 min. mortality at 24 hr. (8) Nembutal (N. Abbott) i.p. 3 ma. Sleeping time was measure immediately. (9) Reserpine (R. Ciba) s.c. 1 ma. Gastric ulcers were apprai sed at death, mortality listed on day Results PCN at 10 mg protected rats against the toxic effects of A, CZ, C, G. I, K, LSD, N and R. whereas 200 mcg T sensitized them, except to N. PCN at 1 mg was no longer protective against G and R. T -50 mcg did not sensitize rats to CZ, G and K. 10 mg PCN and 50 mcg T antagonized each other only in A-intoxicated rats. With all other toxicants except R. PCN effects were blocked by either T dose. When 1 mg PCN was given with 50 or 200 mcg T. the effects of both decreased. In some cases neither the resistance increasing effect of PCN against CZ, G. LSD and N, nor the aggravating action of T on R and I was altered.
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