naltrindole and 16-methylcyprenorphine

In this study it has been shown that the unexpected increase in food consumption, produced by the alpha 2-adrenoceptor antagonist idazoxan (10 mg/kg, i.p.) in rats, was significantly attenuated by small doses of the opioid antagonist (-)-naloxone (0.1, 1 mg/kg, i.p.) and totally inhibited by a small dose of naltrexone (1 mg/kg, i.p.). On the other hand, idazoxan-induced feeding was not affected by (+)-naloxone (0.1, 1 mg/kg, i.p.), which is inactive at opioid receptors. In addition, idazoxan-induced food consumption was not blocked by the delta-opioid antagonist, naltrindole (0.1, 1 mg/kg, i.p.) nor by the mu/delta-antagonist, RX8008M (16-methyl cyprenorphine; 0.1, 1 mg/kg, i.p.), which clearly discriminates between mu/delta- and kappa-opioid receptor function in vivo. These findings suggest that idazoxan may lead to the release of endogenous opioid peptides, which subsequently stimulate feeding by activation of kappa-, as opposed to mu- or delta-opioid receptors. This response is unlikely to be due to alpha 2-adrenoceptor blockade, since other highly selective alpha 2-adrenoceptor antagonists do not increase food intake and, instead may reflect the high affinity of idazoxan for non-adrenoceptor idazoxan binding sites.

Topics: Adrenergic alpha-Antagonists; Animals; Dioxanes; Dose-Response Relationship, Drug; Eating; Endorphins; Idazoxan; Indoles; Male; Morphinans; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Inbred Strains

The effects of novel opioid antagonists on the behavioural syndrome induced by electroconvulsive shock (ECS) in rats have been examined and compared with those of the established agent naloxone. A single ECS produced catalepsy and significantly increased tail immersion response times during the 15 min following the seizure. These responses were inhibited by a low dose of naloxone (1 mg kg-1, i.p.) and also by RX8008M (16-methylcyprenorphine; 1 mg kg-1, i.p.) which blocks mu- and delta- but not kappa-opioid receptor function. In comparison, the antinociception and catalepsy induced by ECS was not attenuated by the selective delta-receptor antagonist naltrindole (1 mg kg-1, i.p.). These results suggest that ECS-induced antinociception and catalepsy may be mediated by endogenous opioids acting at mu-opioid receptors and are consistent with biochemical studies showing the release of beta-endorphin in both animals and man following this procedure.

Topics: Analgesia; Animals; Catalepsy; Electroshock; Indoles; Injections, Intraperitoneal; Male; Morphinans; Naltrexone; Narcotic Antagonists; Rats; Rats, Inbred Strains; Receptors, Opioid