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

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Abstract
This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzeneacetamidopiperidine and benzeneacetamidopiperazine analogues. 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. 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. It is concluded that the seven novel compounds described are all potent and selective agonists for the κ‐opioid receptor.