Attenuation of some signs of opioid withdrawal by inhibitors of nitric oxide synthase.
Effects of nitric oxide synthase (NOS) inhibitors (L-NG-nitroarginine, L-NG-nitroarginine methyl ester) on precipitated opioid withdrawal were studied in morphine-dependent rats given naloxone, in order to assess the involvement of nitric oxide (NO) in opioid dependence. L-NG-Nitroarginine (7.5 mg/kg, IP, 1 h before naloxone or b.i.d. on days 4-7 of an 8-day morphine treatment) reduced wet dog shakes and weight loss; when given by osmotic pumps (15 mg/kg per day), the drug reduced wet dog shakes but not weight loss. L-NG-Nitroarginine methyl ester (60 mg/kg, 1 h before naloxone) also reduced wet dog shakes and weight loss. The results indicate that NOS inhibitors warrant further study as potential treatments of the opioid withdrawal syndrome.
Kimes
A S
AS
Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224.
Vaupel
D B
DB
London
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ED
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009021:Morphine Dependence / Q000523:psychology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase; D051381:Rats; D011916:Rats, Inbred F344; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology; D015431:Weight Loss / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester