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Vol. 280, Issue 2, 600-605, 1997
)TAN-67, in the Mouse Spinal Cord1
Department of Anesthesiology, Medical College of Wisconsin,
Milwaukee, Wisconsin (L.F.T., M.N., H.M.),
Basic Research Laboratory,
Toray Industries Inc., Kamakura 248, Japan (K.K., A.M., H.N.) and
Departments of
Pathophysiology and Therapeutics, The effects of enantiomorphs of TAN-67
(2-methyl-4a
-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a-octahydro-quinolino[2,3,3-g]isoquinoline), (
)TAN-67 and (+)TAN-67, given intrathecally (i.t.) on antinociceptive 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 its
enantiomer (+)TAN-67 even at smaller doses (1.8, 4.5 and 8.9 nmol)
given i.t. decreased the latencies of the tail-flick response. In
addition, (+)TAN-67 at higher doses (17.9-89.4 nmol) given i.t.
produced scratching 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-binaltorphimine dihydrochloride. Pretreatment with ()TAN-67 given i.t. 3 hr earlier attenuated the tail-flick inhibition induced by
subsequent i.t. administration of ()TAN-67 and by
[D-Pen2,5]enkephalin (DPDPE). However, the
tail-flick inhibition induced by
[D-Ala2]deltorphin II,
[D-Ala2,NMePhe4,Gly5-ol]enkephalin
and U50,488H were not affected by ()TAN-67 pretreatment. Conversely,
pretreatment with DPDPE given i.t. 3 hr earlier attenuated the
tail-flick inhibition induced by subsequent i.t. administration of
()TAN-67 and by DPDPE. However, the tail-flick inhibition induced by
[D-Ala2]deltorphin II was not affected by
i.t. DPDPE pretreatment. It is concluded that ()TAN-67 given i.t.
produces 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.
Copyright © by The American Society for Pharmacology and Experimental Therapeutics
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