%0 Journal Article %A Steve McGaraughty %A Katharine L. Chu %A Carol T. Wismer %A Joe Mikusa %A Chang Z. Zhu %A Marlon Cowart %A Elizabeth A. Kowaluk %A Michael F. Jarvis %T Effects of A-134974, a Novel Adenosine Kinase Inhibitor, on Carrageenan-Induced Inflammatory Hyperalgesia and Locomotor Activity in Rats: Evaluation of the Sites of Action %D 2001 %J Journal of Pharmacology and Experimental Therapeutics %P 501-509 %V 296 %N 2 %X The present study investigated 1) antihyperalgesic actions of a novel and selective adenosine kinase (AK) inhibitor, A-134974 (IC50 = 60 pM), in the carrageenan model of thermal hyperalgesia; 2) effects of A-134974 on locomotor activity; and 3) relative contributions of supraspinal, spinal, and peripheral sites to the actions of A-134974. Systemic A-134974 (i.p.) dose dependently reduced hyperalgesia (ED50 = 1 μmol/kg) and at higher doses, reduced locomotor activity (ED50 = 16 μmol/kg). Administration of A-134974 intrathecally (i.t.) was more potent (ED50 = 6 nmol) at producing antihyperalgesia than delivering the compound by intracerebralventricular (ED50 = 100 nmol, i.c.v.) or intraplantar (ED50 >300 nmol) routes. In contrast, i.c.v. administration of A-134974 was more effective in reducing locomotor activity than i.t. administration (ED50 values were 1 and >100 nmol, respectively). Increasing the pretreatment time for i.t.-delivered A-134974 caused a greater reduction in locomotor activity (ED50 = 10 nmol). This was due to diffusion of A-134974 (i.t.) to supraspinal sites. The antihyperalgesic effects of systemic A-134974 were antagonized by the adenosine receptor antagonist theophylline (THEO, 30–500 nmol) administered i.t., but not i.c.v. In the locomotor assay, i.t.-injected THEO did not antagonize hypomobility caused by systemic or i.t. administration of A-134974. However, i.c.v. infusion of THEO did block the hypomotive actions of i.c.v.-, i.t.-, and i.p.-administered A-134974. These data demonstrate that the novel AK inhibitor A-134974 potently reduces thermal hyperalgesia primarily through interactions with spinal sites, whereas its ability to depress locomotor activity is predominantly mediated by supraspinal sites. %U https://jpet.aspetjournals.org/content/jpet/296/2/501.full.pdf