作者: P.K. Moore , P. Wallace , Z. Gaffen , S.L. Hart , R.C. Babbedge
DOI: 10.1111/J.1476-5381.1993.TB13795.X
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摘要: 1. 7-Nitro indazole (7-NI, 10-50 mg kg-1), 6-nitro and (25-100 kg-1) administered i.p. in the mouse produce dose-related antinociception late phase of formalin-induced hindpaw licking acetic acid-induced abdominal constriction assays. The ED50 values (mg were as follows: 7-NI (27.5 22.5), (62.5 44.0) (41.0 48.5) two assays respectively. 3-Indazolinone, 6 amino 6-sulphanilimido (all 50 without effect. With exception 5-nitro (50 which produced sedation, none other derivates examined caused overt behavioural changes. 2. antinociceptive effect (25 kg-1, i.p.) assay was partially (46.7 +/- 16.2%, n = 18) reversed by pretreatment with L- but not D-arginine (both i.p.). 3. time course induced correlated inhibition brain (cerebellum) nitric oxide synthase (NOS) activity. Maximum activity NOS detected 18-30 min following administration. In contrast, no or cerebellar 75 post-injection. 4. 7-NI, indazole, 3-indazolinone 6-amino failed to influence mean arterial pressure (MAP) over 45 after administration anaesthetized mouse. Similarly, i.v. rat did increase MAP vasodepressor injected acetylcholine (ACh) same period.5. (100 microM) vasorelaxant ACh (IC50, 0.2 0.04 microM, cf. 0.16+/-0.06 6) phenylephrine-precontracted rabbit aortic rings.6. These data provide further evidence that results from central is associated vivo vascular endothelial cells NOS. Accordingly, (or a derivative thereof) may an alternative approach development novel drugs.