A novel series of potent and selective agonists at the opioid kappa-receptor.
Three novel opioid agonists are described. These compounds were found to bind with high affinity and selectivity to the kappa-opioid receptor. Isolated tissue studies using the field-stimulated mouse vas deferens and guinea-pig ileum preparations confirmed the high agonist potency and naloxone-reversibility of these agents. All three compounds exhibited potent antinociceptive activity in the mouse abdominal constriction model. These compounds should prove useful as tools to investigate kappa-receptor function.
Costello
G F
GF
Bioscience Department, ICI Pharmaceuticals Division, Macclesfield, Cheshire, U.K.
Main
B G
BG
Barlow
J J
JJ
Carroll
J A
JA
Shaw
J S
JS
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001575:Benzomorphans / Q000378:metabolism*; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D051379:Mice; D009019:Morphinans / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009270:Naloxone / Q000378:metabolism*; D009294:Narcotics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017473:Receptors, Opioid, kappa
D001575:Benzomorphans; D009019:Morphinans; D009294:Narcotics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C058467:ICI 197067; C058468:ICI 199441; C058469:ICI 204879; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C027248:bremazocine