Cholecystokinin octapeptide (CCK-8), ceruletide and analogues of ceruletide: effects on tremors induced by oxotremorine, harmine and ibogaine. A comparison with prolyl-leucylglycine amide (MIF), anti-Parkinsonian drugs and clonazepam.
Neuropharmacology June 1, 1983 DOI: 10.1016/0028-3908(83)90100-4 via PubMed
Summary
AI-generated from the abstractCholecystokinin octapeptide (CCK-8), ceruletide, and ten of its analogues were more potent than several standard drugs (atropine, haloperidol, and others) at suppressing tremors caused by harmine or ibogaine in mice. However, these peptides were inactive against oxotremorine-induced tremors. The tremorolytic effect appeared independent of other central actions like hypothermia or sedation, suggesting CCK-like peptides may play a physiological role in regulating extrapyramidal motor activity.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | CCK-8 ceruletide prolyl-leucylglycine amide atropine haloperidol biperiden ethopropazine trihexyphenidyl methixene clonazepam |
| Duration | Antagonists given 10 min (in some trials 30 min) before the tremorogen |
| Citations | 18 |
| Key finding | CCK-8 and ceruletide, along with many ceruletide analogues, showed greater potency than reference drugs in suppressing harmine- and ibogaine-induced tremors in mice, but were inactive against oxotremorine-induced tremors. |
Abstract
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.