Bremazocine differentially antagonizes responses to selective mu and delta opioid receptor agonists in rat hippocampus.
The effects of mu, delta and kappa opioid receptor agonists were examined on evoked field potentials in brain slices prepared from rat hippocampus. The effects of the mu-selective opioid peptide [D-Ala2, NMe-Phe4, Met(O)5ol]enkephalin (FK 33-824) and the delta-selective peptide [D-Pen2, D-Pen5]enkephalin (DPDPE) were qualitatively and quantitatively similar. Both increased the amplitude of evoked population spike responses when perfused in low nanomolar concentrations in a fashion consistent with what has been previously reported for other opiate agonists such as morphine. The kappa-selective agonists bremazocine and U-50, 488H were without effect upon evoked responses at concentrations as high as 10 microM. Bremazocine, but not U-50, 488H, proved to be an extremely potent antagonist of responses to both mu- and delta- selective agonists. Moreover, bremazocine was considerably more potent in antagonizing responses to FK 33-824 than DPDPE, which supports the hypothesis that FK 33-824 and DPDPE act via different receptors. Thus, although bremazocine is an agonist at kappa receptors, it appears to act as an antagonist at other opioid receptor sites.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004558:Electric Stimulation; D004566:Electrodes; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D001575:Benzomorphans; D004745:Enkephalins; D009019:Morphinans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; C027248:bremazocine