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-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-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 receptor.
Tseng
L F
LF
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Narita
M
M
Mizoguchi
H
H
Kawai
K
K
Mizusuna
A
A
Kamei
J
J
Suzuki
T
T
Nagase
H
H
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006930:Hyperalgesia; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain; D010147:Pain Measurement; D011759:Pyrrolidines / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D004745:Enkephalins; D011759:Pyrrolidines; D011804:Quinolines; D017465:Receptors, Opioid, delta; C094142:TAN 67; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-