The production of an alternative laboratory model of the Parkinson syndrome using a new benzylimidoylurea derivative LON 954.
N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON 954) causes a reproducible rest tremor in mice, of rapid onset and short duration with no associated rigidity or akinesia and in the absence of any marked changes in body temperature or accompanying peripheral parasympathomimetic effects. This tremor can be antagonised by the dopamine receptor agonists L-Dopa, bromocriptine, nomifensine and piribedil, as well as by anticholinergic anti-Parkinson drugs having an inhibitory effect on dopamine uptake such as benapryzine and benztropine. In contrast, benzhexol, orphenadrine and amantadine had no effect. LON 954 appears to be more specific than oxotremorine for the detection of drugs having therapeutic potential in the treatment of Parkinson's disease, particularly those exerting their effect through dopaminergic systems. An antagonist (BS 100-141), which is a structural isomer of LON 954, is also described.
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D007536:Isomerism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000188:drug therapy; D012995:Solubility; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000978:Antiparkinson Agents; D001562:Benzimidazoles; D010095:Oxotremorine; C014908:LON 954; D014508:Urea