The modulatory effect of (+)-TAN-67 on the antinociceptive effects of the nociceptin/orphanin FQ in mice.
To clarify the pharmacological properties of (+)2-Methyl-4aalpha-(3-hydroxyphenyl)-1, 2, 3, 4, 4a, 5, 12, 12aalpha-octahydro-quinolino[2, 3, 3-g]isoquinoline ((+)-TAN-67), the effect of (+)-TAN-67 on the antinociception induced by the intrathecal (i.t.) administration of nociceptin/orphanin FQ was studied in mice using the tail-flick test and the formalin test. I.t. administration of (+)-TAN-67, at doses of 1 to 10 ng, facilitated the tail-flick response in a dose-dependent manner in mice. In addition, i.t. administration of (+)-TAN-67 (1 to 10 ng) in mice produced a marked pain-like aversive responses. I.t. pretreatment with D-Pro(9)-[spiro-gamma-lactam]-Leu(10)-Trp(11)-physalaemin(1-11) (GR82334, 0.1-1.0 nmol), a potent and selective tachykinin NK(1) receptor antagonist, dose-dependently blocked the reduction of the tail-flick response induced by (+)-TAN-67. Furthermore, (+)-TAN-67-induced facilitation of the tail-flick response was abolished in capsaicin-treated mice. On the other hand, (+)-TAN-67-induced flinching responses were dose-dependently and significantly reduced by i.t. pretreatment with GR82334 (0.1-1.0 nmol). The duration of i.t. (+)-TAN-67-induced flinching responses was significantly reduced in capsaicin-treated mice as compared with naive mice. I.t. administration of nociceptin/orphanin FQ (1-10 nmol) dose-dependently increased the tail-flick latency. I.t. administration of nociceptin/orphanin FQ (0.1-1.0 nmol) significantly and dose-dependently reduced the first-phase nociceptive response, but not the second-phase nociceptive response. I.t. pretreatment with (+)-TAN-67 (0.3-3.0 microg) for 30 min dose-dependently attenuated the antinociception induced by i.t. nociceptin (10 nmol) in the tail-flick test. Furthermore, the antinociceptive effect of nociceptin/orphanin FQ (1 nmol, i.t.) on the first-phase response in the formalin test was dose-dependently attenuated by s.c. pretreatment with (+)-TAN-67 (0.3-3.0 microg). (+)-TAN-67 (0.3-3.0 microg, i.t.), by itself, did not facilitate the tail-flick response or produce apparent behavioral changes. It is possible that (+)-TAN-67 has an antagonistic effect on nociceptin/orphanin FQ-induced antinociception.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, Japan. kamei@hoshi.ac.jp
Ohsawa
M
M
Suzuki
T
T
Saitoh
A
A
Endoh
T
T
Narita
M
M
Tseng
L F
LF
Nagase
H
H
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018847:Opioid Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D010803:Physalaemin / Q000031:analogs & derivatives / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D000097629:Nociceptin
D000700:Analgesics; D018847:Opioid Peptides; D010803:Physalaemin; D011804:Quinolines; D011957:Receptors, Opioid; D018039:Receptors, Tachykinin; D000097629:Nociceptin; C094142:TAN 67; C079014:GR 82334