Acquired tolerance to intravenous thiobarbiturates in animals.

SEEVERS (1954) has defined tolerance to and vice versa. The author has verified narcotics as "the partial or complete this with thiopentone, thialbarbitone, immunity to quantities of these substances thiamylal and hexobarbitone. which would otherwise diminish or com-In the course of clinical work the pletely abolish the functional activity of author has encountered several cases of certain neurophysiological and other tolerance to thiobarbiturates, in which the mechanisms." The repeated administra-patients had been receiving large doses of tion of medium-acting barbiturates leads sedative or analgesic drugs. In none of to the development of tolerance to their these patients could the resistance be narcotic effects. This applies to amylobar-attributed to acquired tolerance to bitone and isopropyl-P-bromallyl-barbitu-medium-acting barbiturates. Similarly the rate in rabbits (Fitch, 1930) and delvinal drugs being administered to each of the and pentobarbitone in guineapigs and rats resistant patients varied daily, but in each (Carmichael, 1941, 1948). The above case they were limited to one type of drug workers and Gruber and Keyser (1946) such as D.D.A. analgesics or aspirin-like have convincingly demonstrated that analgesics. tolerance to one barbiturate produces a Experiments were carried out in dogs cross tolerance to other drugs of the same and rats to see if the daily administration series. of one type of sedative or analgesic did, in Mice develop a tolerance to the daily fact, increase the tolerance to thiobarbitu-administration of thiopentone. This effect rates. All thiobarbiturates were given by is maximal in five to six days and amounts the intraperitoneal route, and during the to a decrease in sleeping time by about experiment the interval between these fifty per cent (Hubbard and Goldbaum, injections was such as to avoid tolerance 1949). Thrice weekly administrations of from the drugs themselves. Several con-thiopentone to the dog lead to a forty per trol readings were done before the daily cent decrease in the duration of sleep by administration of sedatives or analgesics the end of the third week (Dundee, 1953). was started. All medication was stopped Green and Koppanyi (1944) found that for 24 hours before injection of the thio-dogs rendered tolerant to thiopentone barbiturates, but drugs were frequently showed cross tolerance to hexobarbitone given when the animals wakened. At the 165