Comparison of 7-nitroindazole with other nitric oxide synthase inhibitors as attenuators of opioid withdrawal |
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Authors: | D Bruce Vaupel Alane S Kimes Edythe D London Edythe D London |
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Institution: | (1) Neuroimaging and Drug Action Section, Intramural Research Program, National Institute on Drug Abuse, 21224 Baltimore, MD, USA;(2) Department of Radiology, Johns Hopkins Medical Institutions and Department of Pharmacology and Experimental Therapeutics, School of Medicine, University of Maryland, Baltimore, MD, USA |
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Abstract: | Previously, we demonstrated that two nonselective inhibitors of nitric oxide synthase (NOS),l-N
G-nitroarginine (l-NNA) andl-N
G-nitroarginine methyl ester (l-NAME), reduced some signs of morphine withdrawal in rats. The present work extended these studies to include 7-nitroindazole (7-NI), an inhibitor specific for cerebral NOS, andN(5)-(1-iminoethyl)-l-ornithine (l-NIO), a potent inhibitor of endothelial NOS. Behavioral effects of these four NOS inhibitors and clonidine, an
2-adrenoceptor, agonist, on morphine withdrawal in rats were assessed. Rats received one 75-mg morphine pellet subcutaneously (SC). Three days later, NOS inhibitors were administered IP 1 h before withdrawal was precipitated with naloxone (0.5 mg/kg, SC) and scored. 7-NI,l-NIO,l-NAME andl-NNA produced dose-related decreases in weight loss, diarrhea, wet dog shakes and grooming. 7-NI also reduced mastication, salivation and genital effects. Clonidine produced effects similar to 7-NI. In awake, morphine-naive and morphine-dependent rats not subjected to withdrawal, 7-NI was the only NOS inhibitor that did not increase blood pressure. Because 7-NI attenuated more signs of opioid withdrawal thanl-NNA,l-NAME orl-NIO without causing hypertension, 7-NI appears to warrant further testing as a potential candidate for human use.Abstracts were presented at the annual meetings of the College on Problems of Drug Dependence, West Palm Beach, Fla., 18–23, June 1994; International Narcotics Research Conference, North Falmouth, Cape Cod, Mass., 16–21, July 1994; and a Satellite Symposium to IUPHAR, Montreal, Canada, 22–24, July 1994. |
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Keywords: | Nitric oxide synthase Morphine Dependence Opioid withdrawal 7-Nitroindazole l-Iminoethyl ornithine" target="_blank">l-Iminoethyl ornithine l-N
G-Nitroarginine" target="_blank">l-N
G-Nitroarginine Nitric oxide Rats Blood pressure |
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