Central effects of ceruletide analogues.

Ten ceruletide analogues and cholecystokinin octapeptide (CCK-8) were compared with ceruletide regarding neuropharmacological effects in mice after peripheral administration. The effects under study were inhibition of motor response to noxious stimulation (hot plate), production of ptosis, inhibition of exploratory rearing activity, elevation of threshold for picrotoxin-induced convulsions, and antagonism of methylphenidate-induced gnawing. Desulfation, deamidation and shortening of the peptide chain by five amino acids destroyed all pharmacological activities of ceruletide. Other modifications were of unequal consequences for the pharmacological profile of a given analogue, decreasing some effects while increasing others. Hence, structural changes of the ceruletide molecule resulted in modulations of both potency and selectivity.