cholecystokinin and Blepharoptosis

Topics: Analgesics; Animals; Anticonvulsants; Blepharoptosis; Body Temperature; Brain; Catalepsy; Cholecystokinin; Conditioning, Psychological; Humans; Hypnotics and Sedatives; Self Stimulation; Stereotyped Behavior; Structure-Activity Relationship; Tremor

Cholecystokinin octapeptide (CCK-8), caerulein and diazepam inhibited exploratory rearing activity and harman-induced convulsions in mice. Pretreatment with the selective benzodiazepine receptor antagonist Ro 15-1788, reduced or abolished the sedative and anticonvulsive effects of diazepam, but left the same effects of both peptides unaffected. The peptide-induced ptosis was even increased by Ro 15-1788. The results suggest that the CCK-like peptides do not directly interact with the benzodiazepine receptor.

Topics: Animals; Anticonvulsants; Benzodiazepinones; Blepharoptosis; Body Temperature; Ceruletide; Cholecystokinin; Diazepam; Flumazenil; Harmine; Hypnotics and Sedatives; Male; Mice; Peptide Fragments; Seizures; Sincalide

The antinociceptive effect in mice (hot-plate test) of caerulein (0.15 mg/kg s.c.) was many times more resistant to naloxone than that of morphine (2 mg/kg s.c., equipotent with the caerulein dose). The ED50 (mg/kg s.c.) of naloxone (given simultaneously with an agonist) was with morphine 0.01 and with caerulein 0.07. When administered intravenously after the agonist, the ED50 (mg/kg i.v.) against morphine was 0.012 and that against caerulein was 0.62. In either type of experiment the dose-response lines of naloxone against caerulein were very shallow as compared with those against morphine. A caerulein dose of 5 micrograms/kg enhanced the antinociceptive effect of morphine only when given before morphine, but not when given after it. The limited additivity of the effects together with the different susceptibility to naloxone of the antinociceptive actions indirectly suggest that caerulein and morphine do not share the same mechanism of action. Palpebral ptosis occurred only after caerulein and was completely resistant to naloxone 8 mg/kg s.c.

Topics: Analgesics; Animals; Blepharoptosis; Ceruletide; Cholecystokinin; Hemodynamics; Male; Mice; Morphine; Naloxone; Rats; Rats, Inbred Strains

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.

Topics: Analgesia; Animals; Anticonvulsants; Behavior, Animal; Blepharoptosis; Brain; Ceruletide; Cholecystokinin; Dose-Response Relationship, Drug; Humans; Hypnotics and Sedatives; Male; Mice; Peptide Fragments; Sincalide; Stereotyped Behavior; Structure-Activity Relationship

Topics: Analgesics; Animals; Blepharoptosis; Catalepsy; Ceruletide; Cholecystokinin; Dose-Response Relationship, Drug; Drug Tolerance; Humans; Male; Mice; Pentagastrin; Reaction Time; Sincalide; Time Factors