A series of novel, highly potent and selective agonists for the κ‐opioid receptor

1 This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzeneacetamidopiperidine and benzeneacetamidopiperazine analogues. 2 These compounds all showed potent, naloxone‐reversible, full agonist activiy in the field‐stimulated rabbit vas deferens, indicating that they are κ‐opioid agonists; but showed very little activity in the rat or hamster vas deferens, indicating good selectivity with regard to μ‐ and δ‐opioid receptors. 3 They were all potent antinociceptive agents, the most potent compound, GR103545, having an ED50 value in the mouse abdominal constriction test of 0.25 μg kg−1 s.c. The compounds also produced sedation and diuresis, but had little effect on respiration rate or gastrointestinal motility. 4 It is concluded that the seven novel compounds described are all potent and selective agonists for the κ‐opioid receptor.