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.
References
Jul 21, 1992·European Journal of Pharmacology·A KawabataH Takagi
Feb 11, 1992·European Journal of Pharmacology·A IalentiM Di Rosa
Oct 15, 1990·The Biochemical Journal·M Murphy
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M W RadomskiS Moncada
Jul 1, 1994·British Journal of Pharmacology·D Minc-GolombJ P Schwartz
Jun 20, 1995·Archives of Biochemistry and Biophysics·D W Reif, S A McCreedy
Feb 1, 1993·British Journal of Pharmacology·P K MooreS L Hart
May 1, 1994·Neuroscience·S T MellerG F Gebhart
Feb 1, 1993·Pain·S T Meller, G F Gebhart
Jul 1, 1996·British Journal of Pharmacology·S PfeifferB Mayer
Aug 1, 1996·Pain·J X Hao, X J Xu
Oct 12, 1999·Journal of Neuroscience Methods·E D MilliganL R Watkins
Feb 7, 2001·Biochemical and Biophysical Research Communications·M NakaN Taniguchi
Aug 10, 2000·American Journal of Respiratory and Critical Care Medicine·I OkamotoK Tanaka
Feb 13, 2001·European Journal of Pharmacology·Y NaitoT Yoshikawa
Mar 30, 2001·Neuroreport·A KawabataH Nishikawa
Nov 28, 2002·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Daisuke OgawaHirofumi Makino
May 30, 2003·Pharmacological Reviews·Noboru Toda, Tomio Okamura
Oct 22, 2003·Journal of the Neurological Sciences·Satoshi ShibutaTakashi Mashimo
Dec 5, 2003·Life Sciences·Yoshihisa KamanakaNaoyuki Kawao
Citations
Dec 2, 2008·Nature Reviews. Drug Discovery·Inki KimJohn C Reed
Nov 3, 2012·Marine Drugs·Shi-Ying HuangZhi-Hong Wen
Sep 18, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li-Chai ChenZhi-Hong Wen
Dec 9, 2014·Molecular Neurobiology·Venkata Prasuja NakkaRaghu Vemuganti
Apr 29, 2008·European Journal of Pharmacology·Linda S SorkinDanielle B Nanigian
Mar 31, 2007·European Journal of Pain : EJP·Michael Karl BoettgerClaudia Sommer
Mar 17, 2006·Free Radical Biology & Medicine·Masayoshi AbeKeiichi Tanaka
Apr 5, 2016·Brain Research Bulletin·Wei HuYanguo Hong
Jun 8, 2006·Osteoarthritis and Cartilage·Y XiangT Kato
Jun 19, 2012·European Journal of Medicinal Chemistry·Andrea Pozo-RodrigálvarezJavier Pérez-Castells
Aug 21, 2014·PloS One·Shi-Ying HuangZhi-Hong Wen
Nov 18, 2017·International Journal of Molecular Sciences·Chieh-Chih ShihZhi-Hong Wen
Jun 14, 2019·Medicinal Research Reviews·Maris A CinelliRichard B Silverman
Jun 15, 2007·The Journal of Pharmacology and Experimental Therapeutics·Giuseppe D'AgostinoAntonio Calignano
Feb 2, 2021·Experimental Biology and Medicine·Lillian HallmarkZenaide Mn Quezado