DELTA-1 OPIOID RECEPTOR-MEDIATED ANTINOCICEPTIVE PROPERTIES OF A NONPEPTIDIC DELTA-OPIOID RECEPTOR AGONIST, (-)TAN-67, IN THE MOUSE SPINAL-CORD

The effects of enantiomorphs of TAN-67 (2-methyl-4a alpha-(3-hydroxyph enyl)-1 ,2,3,4,4a,5,12,12a alpha-octahydro-quinolino[2,3,3-g]isoquinol ine), (-)TAN-67 and (+)TAN-67, given intrathecally (i.t.) on antinocic eptive response with the tail-flick test were studied in male ICR mice . (-)TAN-67 at doses from 17.9 to 89.4 nmol given i.t, produced a dose - and time-dependent inhibition of the tail-flick response, whereas it s enantiomer (+)TAN-67 even at smaller doses (1.8, 4.5 and 8.9 nmol) g iven i.t, decreased the latencies of the tail-flick response. In addit ion, (+)TAN-67 at higher doses (17.9-89.4 nmol) given i.t, produced sc ratching and biting pain-like responses. The antinociceptive response induced by i.t.-administered (-)TAN-67 was mediated by the stimulation of delta-1 but not by delta-2, mu or kappa opioid receptors, because the effect was blocked by the i.t, pretreatment with BNTX, but not by naltriben, [D-Phe-Cys-Tyr-[D-Try-Orn-Thr-Pen-Thr-NH2 or nor-binaltorph imine dihydrochloride. Pretreatment with (-)TAN-67 given i.t. 3 hr ear lier attenuated the tail-flick inhibition induced by subsequent i.t. a dministration of (-)TAN-67 and by [D-Pen(2,5)]enkephalin (DPDPE). Howe ver, the tail-flick inhibition induced by [D-Ala(2)]deltorphin II, [D- Ala(2),NMePhe(4),Gly(5)-ol]enkephalin and U50,488H were not affected b y (-)TAN-67 pretreatment. Conversely, pretreatment with DPDPE given i. t. 3 hr earlier attenuated the tail-flick inhibition induced by subseq uent i.t, administration of (-)TAN-67 and by DPDPE. However, the tail- flick inhibition induced by [D-Ala(2)]deltorphin II was not affected b y i.t. DPDPE pretreatment. It is concluded that (-)TAN-67 given i.t. p roduces delta-1 opioid receptor-mediated antinociception; on the other hand, its enantiomer (+)TAN-67 produces hyperalgesia. Present studies provide other evidence that delta-1 opioid receptors exist separated from delta-2 opioid receptors.