ceruletide and Tremor

The decapeptide from the frog Hyla caerulea, caerulein (caerulein diethylammonium hydrate, ceruletide, CER) is chemically closely related to the C-terminal octapeptide of cholecystokinin (CCK-8). Like CCK-8, CER and some of its analogues produce many behavioural effects in mammals: inhibition of intake of food and water; antinociception; sedation; catalepsy; ptosis, antistereotypic, anticonvulsive and tremorolytic effects; inhibition of self-stimulation. Effects of CER in man comprise sedation, satiety, changes in mood, analgesia and antipsychotic effects. A modulation of central dopaminergic functions appears to be one possible mechanism of CER and its analogues. A common denominator for all effects of CER is, at present, not evident.

Topics: Animals; Anticonvulsants; Avoidance Learning; Behavior, Animal; Blepharoptosis; Body Temperature Regulation; Catalepsy; Ceruletide; Drinking Behavior; Electrophysiology; Feeding Behavior; Humans; Hypnotics and Sedatives; Motor Activity; Pain; Psychotic Disorders; Self Stimulation; Sleep; Stereotyped Behavior; Structure-Activity Relationship; Substance-Related Disorders; Tremor

Two men, aged 63 and 71 years, developed a gross action tremor and dysesthesias several months after an intracerebral hemorrhage. CT and MRI showed a small hemorrhage in the posterior region of the lateral nucleus of the thalamus in each patient. The tremor occurred on movement, had frequencies of 2.5-4.5 Hz and the amplitude varied depending on the joint position of the limb. Ceruletide (a cholecystokinin analog) 0.8 micrograms/kg i.m. produced a marked reduction in the action tremor and improved motor function. This effect appeared 10-15 min after the injection, and lasted for up to 4 weeks. It is suggested that ceruletide may be of value in the treatment of action tremors following a thalamic lesion.

Topics: Aged; Cerebral Hemorrhage; Ceruletide; Humans; Male; Middle Aged; Thalamic Nuclei; Tremor

Cholecystokinin octapeptide (CCK-8), ceruletide (caerulein, CER) and 10 analogues of ceruletide, were studied in mice for antagonism of the tremors induced by harmine (5 mg/kg, s.c.), ibogaine (20 mg/kg, s.c.) and oxotremorine (0.2 mg/kg, s.c.). The following reference drugs were tested for comparison: prolyl-leucylglycine amide (MIF), atropine, haloperidol, biperiden, ethopropazine, trihexyphenidyl, methixene and clonazepam. All treatments were subcutaneous, the antagonists being given 10 min (in some trials 30 min) before the tremorogen. Tremorolytic potency (ED50) was calculated from dose-response curves. Against the tremors induced by either harmine or ibogaine, CCK-8 and ceruletide, as well as many of the analogues of ceruletide had greater tremorolytic potency than the reference drugs. Against oxotremorine, however, ceruletide and its most potent analogue, Nle8-CER (other analogues were not tested) were inactive and MIF showed very little effectiveness. Additional experiments on hypothermia and sedation as well as evaluation of previous studies on other central actions suggested that the tremorolytic effect of CCK-like peptides is independent of other central effects. The CCK-like peptides may play a physiological role in the regulation of extrapyramidal motor activity.

Topics: Alkaloids; Animals; Antiparkinson Agents; Benzodiazepinones; Ceruletide; Cholecystokinin; Clonazepam; Drug Antagonism; Harmine; Hypnotics and Sedatives; Ibogaine; Male; Mice; Mice, Inbred Strains; Oligopeptides; Oxotremorine; Peptide Fragments; Sincalide; Structure-Activity Relationship; Tremor