RT Journal Article
SR Electronic
T1 Tolerance and physical dependence to a short-acting benzodiazepine, midazolam.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1125
OP 1133
VO 252
IS 3
A1 N R Boisse
A1 N Quaglietta
A1 G M Samoriski
A1 J J Guarino
YR 1990
UL http://jpet.aspetjournals.org/content/252/3/1125.abstract
AB Midazolam is a new ultra short-acting benzodiazepine whose physical dependence properties have not been well characterized. Our laboratory has demonstrated previously that physical dependence to the long-acting chlordiazepoxide in the rat is inducible by a single intoxicating dose, whereas maximal dependence required chronically equivalent maximally tolerable dosing b.i.d. for 5 weeks. Based on the methods developed in our laboratory to quantify benzodiazepine intoxication and withdrawal, Trs were designed to evaluate midazolam's capacity to induce dependence in the rat after definable acute (120 mg/kg p.o.), sub-acute (120 mg/kg q.i.d. x 3 days) and chronic (120-180 mg/kg bid. x 5 weeks) dosing that was near maximally tolerable. A single dose of midazolam failed to produce withdrawal signs. Tolerance and dependence increased as a function of midazolam dose and duration of Tr.