Supraspinal and spinal potency of selective opioid agonists in the XXXX writhing test.

@entity7862 @entity19 @entity11053 @entity57742 @entity1286 @entity19035 @entity1543
Three agonists with the highest degree of selectivity available for mu ( @entity7862 , @entity7862 ), delta ([ D- @entity19035 ,D-Pen5]enkephalin, DPDPE) and kappa (U-50,488H, U50) opioid receptors were compared for their activity in inhibiting @entity1543 -induced writhing in @entity19 . Additionally, three reference agonists for mu ( @entity1286 ), delta ([ D-Ala2,D-Leu5]enkephalin, DADLE) and kappa ( @entity57742 , KC) receptors were also studied in this test. The agonists were given directly into the lateral cerebral ventricle (i.c.v.) or into the lumbar spinal subarachnoid space (intrathecal), and the potency of each compound was compared across injection sites and with data previously obtained in a thermal analgesic test ( @entity19 hot-plate test). The rank order of potency for inhibition of writhing after i.c.v. administration was @entity7862 greater than DADLE greater than @entity1286 greater than DPDPE; KC and U50 showed no significant activity by this route. After intrathecal administration, the compounds inhibited writhing with a rank potency order of @entity7862 greater than KC greater than @entity1286 = @entity11053 greater than DPDPE greater than U50. All compounds were more potent in inhibiting writhing at spinal sites than at supraspinal sites; DPDPE and @entity7862 were 15 and 24 times more potent after intrathecal than after i.c.v. administration, respectively. The proposed delta agonists DPDPE and DADLE inhibited writhing at both spinal and supraspinal sites. Further, although the proposed kappa-acting compounds KC and U50 were effective at relatively low doses at spinal levels, these compounds lacked activity at supraspinal sites at doses not causing sedation.(ABSTRACT TRUNCATED AT 250 WORDS)
