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

Neuroscience Letters
Fumiko SekiguchiAtsufumi Kawabata

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.

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Citations

Dec 2, 2008·Nature Reviews. Drug Discovery·Inki KimJohn C Reed
Sep 18, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li-Chai ChenZhi-Hong Wen
Mar 31, 2007·European Journal of Pain : EJP·Michael Karl BoettgerClaudia Sommer
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Jun 19, 2012·European Journal of Medicinal Chemistry·Andrea Pozo-RodrigálvarezJavier Pérez-Castells
Nov 18, 2017·International Journal of Molecular Sciences·Chieh-Chih ShihZhi-Hong Wen
Jun 14, 2019·Medicinal Research Reviews·Maris A CinelliRichard B Silverman
Feb 2, 2021·Experimental Biology and Medicine·Lillian HallmarkZenaide Mn Quezado

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