Rational drug design and synthesis of a selective ε opioid receptor antagonist on the basis of the accessory site concept

To newly synthesize a selective ε opioid receptor antagonist, 17-(cyclopropylmethyl)-4,5α-epoxy-6β,21-epoxymethano-3-hydroxy-6,14-endoethenomorphinan-7α-(N-phenethyl)carboxamide was first designed from an ε opioid receptor agonist TAN-821 on the basis of the accessory site concept. The designed compound antagonized the agonistic effects induced by an ε opioid receptor agonist β-endorphin on the rat vas deference test. Moreover, the designed compound blocked the antinociception induced by β-endorphin given intracerebroventricularly.