SNC 80, a selective, nonpeptidic and systemically active opioid delta agonist.
The present study has investigated the pharmacology of SNC 80, a nonpeptidic ligand proposed to be a selective delta agonist in vitro and in vivo. SNC 80 was potent in producing inhibition of electrically induced contractions of mouse vas deferens, but not in inhibiting contractions of the guinea pig isolated ileum (IC50 values of 2.73 nM and 5457 nM, respectively). The delta selective antagonist ICI 174,864 (1 microM) and the mu selective antagonist CTAP (1 microM) produced 236- and 1.9-fold increases, respectively, in the SNC 80 IC50 value in the mouse vas deferens. SNC 80 preferentially competed against sites labeled by [3H]naltrindole (delta receptors) rather than against those labeled by [3H]DAMGO (mu receptors) or [3H]U69, 593 kappa receptors) in mouse whole-brain assays. The ratios of the calculated Ki values for SNC 80 at mu/delta and kappa/delta sites were 495- and 248-fold, respectively, which indicates a significant degree of delta selectivity for this compound in radioligand binding assays. SNC 80 produced dose- and time-related antinociception in the mouse warm-water tail-flick test after i.c.v., i.th. and i.p. administration. The calculated A50 values (and 95% C.I.) for SNC 80 administered i.c.v., i.th. and i.p. were 104.9 (63.7-172.7) nmol, 69 (51.8-92.1) nmol and 57 (44.5-73.1) mg/kg, respectively. The i.c.v. administration of SNC 80 also produced dose- and time-related antinociception in the hot-plate test, with a calculated A50 value (and 95% C.I.) of 91.9 (60.3-140.0) nmol.(ABSTRACT TRUNCATED AT 250 WORDS)
Bilsky
E J
EJ
Department of Pharmacology, University of Arizona, Tucson, USA.
Calderon
S N
SN
Wang
T
T
Bernstein
R N
RN
Davis
P
P
Hruby
V J
VJ
McNutt
R W
RW
Rothman
R B
RB
Rice
K C
KC
Porreca
F
F
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000819:agonists*
D000700:Analgesics; D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D009271:Naltrexone; C055382:naltrindole