7-Benzylidenenaltrexone (BNTX): a selective delta 1 opioid receptor antagonist in the mouse spinal cord.

Recent reports provided evidence that at least two delta opioid receptors may mediate antinociception in mice. In this study, we studied further the involvement of delta opioid receptor subtypes in mediating antinociception at spinal sites in mice using subtype selective agonists and antagonists. The antinociceptive ED50 values (95% C.I.) of i.t. administered DPDPE [(D-Pen2, D-Pen5)enkephalin] (delta 1 receptor agonist) and DELT II [(D-Ala2)deltorphin II] (delta 2 receptor agonist) were 6.3 (5.2-7.6) and 6.4 (5.4-7.7) nmol/mouse, respectively. Administration of BNTX, s.c. increased the antinociceptive ED50 value of DPDPE 5.9-fold whereas that of DELT II was not changed significantly. On the other hand administration of naltriben (NTB, the benzofuran derivative of naltrindole), s.c. increased the antinociceptive ED50 value of DELT II 12.5-fold but did not alter that of DPDPE. Similarly administration of BNTX, i.t. increased the antinociceptive ED50 value of DPDPE 4-fold without altering significantly that of DELT II. NTB given i.t. enlarged the antinociceptive ED50 of DELT II 11-fold without affecting significantly that of DPDPE. BNTX, s.c. did not alter the antinociceptive ED50 values of the mu-agonists, DAMGO [(D-Ala2,MePhe4,Gly-ol5) enkephalin] and morphine or that of the kappa-agonist, U50,488H [trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl-cyclohexyl]benzeneacetamide] These results demonstrate that BNTX is highly selective for delta 1 opioid receptors at spinal sites. Also, the present data provide for the involvement of both delta 1 and delta 2 opioid receptors in mediating antinociception at spinal sites in mice.