Ten ceruletide analogues and cholecystokinin octapeptide (CCK-8) were compared with ceruletide regarding neuropharmacological effects in mice after subcutaneous administration. The effects under study were catalepsy, prolongation of hexobarbital-induced sleep and delay in onset of harman-induced convulsions. Ceruletide and several analogues were more potent than the reference drugs, diazepam and haloperidol. Desulfation, deamidation and shortening of the peptide chain by five amino acids strongly reduced or abolished the pharmacological activities of ceruletide. Other chemical modulations mostly weakened the efficacy, but to an unequal extent for the three effects, which altered the pharmacological selectivity.

Animals↗

PubMedDate not supplied

Ceruletide, ceruletide analogues and cholecystokinin octapeptide (CCK-8): effects on isolated intestinal preparations and gallbladders of guinea pigs and mice.

The smooth muscle stimulatory effects of cholecystokinin octapeptide (CCK-8), ceruletide (CER), ten analogues of CER, and carbachol were studied in isolated organs of the guinea pig and the mouse (stomach, ileum, duodenum, colon and gallbladder). On a molar basis, CCK-8 and CER had in all organs except stomach greater potency (lower EC50) than carbachol. The effectiveness (Emax) of CCK-8 and CER was in the gut less than that of carbachol, in the guinea pig gallbladder equal with and in the mouse gallbladder superior to that of carbachol. The alteration of peptide structure was virtually without influence on effectiveness; however, it greatly modified the potency and the organ selectivity of the effect. There was no clear-cut correlation between the potency to stimulate smooth muscle and to alter the behavior of the mouse.

Animals↗

PubMedDate not supplied

Neuroleptic-like, anticonvulsant and antinociceptive effects of aporphine alkaloids: bulbocapnine, corytuberine, boldine and glaucine.

The aporphine alkaloids bulbocapnine, corytuberine, boldine and glaucine were studied in mice and compared with haloperidol, phenobarbital and morphine. All aporphines inhibited the exploratory rearing activity and elicited palpebral ptosis, catalepsy, hypothermia, and prolonged anesthesia by thiopental. They also reduced nociception (hot plate; phenylquinone-induced writhing) and (except for corytuberine) were anticonvulsant against harman and picrotoxin, but not against bicuculline and pentetrazol; corytuberine was proconvulsant. The aporphines (except for corytuberine) antagonized the apomorphine- and methylphenidate-induced stereotyped gnawing and also the apomorphine-induced climbing activity; corytuberine was prostereotypic. The antignawing effects (including those of haloperidol) were stronger when the antagonists were administered after the agonists (gnawing full-fletched) rather than before them: this led to the speculation of a metaphilic interaction at central site(s). Clonazepam inhibited the antistereotypic effect (vs apomorphine) more potently with the aporphines than with haloperidol. The antinociceptive effect (writhing) of the aporphines was, in contrast to that of morphine, resistant to both naloxone and yohimbine. The latter applied also to the antilicking action in the hot plate test; the antijumping effect of boldine was (like that of morphine) antagonized by both yohimbine and naloxone, whereas that of corytuberine was inhibited only by naloxone and that of bulbocapnine preferentially by yohimbine. Hence, opioid and adrenergic mechanisms are unequally involved in the antinociceptive effects of the aporphines. The present results also showed that licking and jumping (in the hot plate test) are pharmacologically different phenomena. In low doses, the aporphines and haloperidol antagonized the antinociceptive effect of morphine (hot plate); hence, these drugs may be considered partial agonists or partial antagonists, respectively.

Analgesics↗