Pronounced hypothermic synergy between systemic baclofen and NOS inhibitor.
Baclofen was administered to rats systemically (intraperitoneal, i.p.) by itself or with L-NAME. Baclofen (1-7.5 mg/kg, i.p.) evoked dose-dependent hypothermia. L-NAME (50 mg/kg, i.p.) was ineffective. For combined administration, L-NAME increased the relative potency of baclofen (F=10.77, p<0.05), indicating multiplicative interaction and synergism. The present data reveal a surprising and significant interaction between nitric oxide synthase (NOS) and baclofen-induced hypothermia.
Department of Pharmaceutical Sciences and Pharmacology, Temple University School of Pharmacy and Medicine, 3307 North Broad Street, Philadelphia, PA 19140, USA. scott.rawls@temple.edu
Scott M
SM
Rawls
David A
DA
Baron
Teresa
T
Gomez
Kyle
K
Jacobs
Ronald J
RJ
Tallarida
D000818:Animals; D001418:Baclofen / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000633:toxicity; D007035:Hypothermia / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D001418:Baclofen; D019331:NG-Nitroarginine Methyl Ester