Opioid activity of sendide, a tachykinin NK 1 receptor antagonist

Abstract

Sendide, a tachykinin NK 1 receptor antagonist, was tested for antagonism against scratching, biting and licking responses elicited by intrathecal (i.t.) injections of various tachykinin receptor agonists, N-methyl- d-aspartate (NMDA), somatostatin and bombesin, in mice. Tachykinin NK 1 receptor agonists, substance P, physalaemin and septide, produced a characteristic behavioural response, consisting of scratching, biting and licking. The substance P-induced response was reduced by small doses (0.0625–1.0 pmol) of sendide in a dose-dependent manner. The behavioural response elicited by other tachykinin NK 1 receptor agonists, physalaemin and septide, was also reduced significantly by a small dose (1.0 pmol) of sendide. The inhibitory effect of sendide (1.0 pmol) was not affected by pretreatment with the opioid receptor antagonist, naloxone, at doses up to 4.0 mg/kg. Higher doses of sendide were needed to reduce the behavioural response to neurokinin A, a tachykinin NK 2 receptor agonist, neurokinin B, a tachykinin NK 3 receptor agonist and eledoisin, a tachykinin NK 2/NK 3 receptor agonist. Pretreatment with naloxone (2.0 mg/kg, i.p.) significantly antagonized sendide (1024 pmol)-induced inhibition of the behavioural responses to neurokinin A, neurokinin B and eledoisin. The behaviours elicited by i.t. injection of NMDA, somatostatin or bombesin were also reduced by a higher dose (1024 pmol) of sendide and this sendide effect was reversed by naloxone. These findings suggest that sendide at higher doses may possess opioid activity in addition to an antagonistic action at tachykinin NK 1 receptors in the spinal cord.