Abstract
The effects of enantiomorphs of TAN-67 (2-methyl-4aα-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aα-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 bydelta-2, mu or kappaopioid 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-NH2or 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 thatdelta-1 opioid receptors exist separated fromdelta-2 opioid receptors.
Footnotes
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Send reprint requests to: Leon F. Tseng, Ph.D., Medical College of Wisconsin, Anesthesiology, MEB-462c, 8701 Watertown Plank Road, Milwaukee, WI 53226.
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↵1 This work was supported by U.S. Public Service grant DA 03811 from the National Institute on Drug Abuse, National Institutes of Health.
- Abbreviations:
- i.t.
- intrathecal
- i.c.v.
- intracerebroventricular
- (±)TAN-67
- 2-methyl-4aα-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aα-octahydro-quinolino[2,3,3-g]isoquinoline
- NTB
- naltriben
- DPDPE
- [d-Pen2,5]enkephalin
- DAMGO
- [d-Ala2,NMePhe4,Gly5-ol]enkephalin
- CTOP
- d-Phe-Cys-Tyr-d-Try-Orn-Thr-Pen-Thr-NH2
- nor-BNI
- nor-binaltorphimine dihydrochloride
- BNTX
- 7-benzylidenenaltrexone
- U50
- 488H, trans-(±)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cycloxyl] benzeneacetamide
- Received June 21, 1996.
- Accepted October 21, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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