The potent inducible nitric oxide synthase inhibitor ONO-1714 inhibits neuronal NOS and exerts antinociception in rats.

Abstract	We evaluated if ONO-1714, known as an inducible nitric oxide synthase (iNOS) inhibitor, could inhibit neuronal NOS (nNOS) and exert antinociception. ONO-1714 potently inhibited both crude rat cerebellar NOS and recombinant human nNOS in vitro. Systemic ONO-1714 at 1-10 mg/kg suppressed carrageenan-induced thermal hyperalgesia in rats, an effect being equivalent to the antinociception caused by L-NAME or 7-nitroindazole at 25 mg/kg. The same doses of ONO-1714 also caused hypertension. Intrathecal (i.t.) ONO-1714 potently reduced the hyperalgesia, the effective dose range (0.2-0.6 microg/rat) being much lower than the antinociceptive dose (150 microg/rat) of i.t. L-NAME. Thus, ONO-1714 is considered a potent inhibitor of nNOS in addition to iNOS. The distinct relative antinociceptive activities of systemic and i.t. ONO-1714 are attributable to its possible poor blood-brain barrier permeability.
Authors	Fumiko Sekiguchi, Yoko Mita, Yoshihisa Kamanaka, Naoyuki Kawao, Hidekazu Matsuya, Chiyomi Taga, Atsufumi Kawabata
Journal	Neuroscience letters (Neurosci Lett) Vol. 365 Issue 2 Pg. 111-5 (Jul 22 2004) ISSN: 0304-3940 [Print] Ireland
PMID	15245789 (Publication Type: Comparative Study, Journal Article)
Chemical References	7-chloro-3-imino-5-methyl-2-azabicyclo(4.1.0)heptane Amidines Analgesics Heterocyclic Compounds, 2-Ring Indazoles Recombinant Proteins Carrageenan NOS1 protein, human NOS2 protein, human Nitric Oxide Synthase Nitric Oxide Synthase Type I Nitric Oxide Synthase Type II Nos1 protein, rat Nos2 protein, rat 7-nitroindazole NG-Nitroarginine Methyl Ester
Topics	Amidines (administration & dosage, pharmacology) Analgesics (pharmacology) Animals Carrageenan Cerebellum (enzymology) Heating Heterocyclic Compounds, 2-Ring (administration & dosage, pharmacology) Humans Hyperalgesia (chemically induced, drug therapy, enzymology) Indazoles (pharmacology) Injections, Intraperitoneal Injections, Spinal Male NG-Nitroarginine Methyl Ester (pharmacology) Nitric Oxide Synthase (antagonists & inhibitors) Nitric Oxide Synthase Type I Nitric Oxide Synthase Type II Rats Rats, Wistar Recombinant Proteins (antagonists & inhibitors)

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