Modulatory role for CCK-B antagonists in Parkinson's disease.
We examined the ability of selective CCK-A and CCK-B receptor antagonists to induce or modulate the locomotor stimulant effects of dopamine agonists in MPTP-treated squirrel monkeys. Administration of 1-100 micrograms/kg i.p. of either the selective CCK-A receptor antagonist devazepide (MK-329) or the CCK-B receptor antagonist L-365,260 alone failed to stimulate a locomotor response in parkinsonian monkeys. In contrast, treatment with L-365,260 caused a 50-60% potentiation of the locomotor stimulatory effects of L-DOPA or (+)-PHNO. No such modulatory effects were observed following pretreatment with devazepide. We suggest that CCK-B receptor antagonists may be useful adjuncts to existing dopamine replacement therapy for improved management of Parkinson's disease.
Boyce
S
S
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Essex, U.K.
Rupniak
N M
NM
Tye
S
S
Steventon
M J
MJ
Iversen
S D
SD
D000818:Animals; D001570:Benzodiazepinones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002230:Carbidopa / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020109:Devazepide; D015259:Dopamine Agents / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D020267:MPTP Poisoning; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010078:Oxazines / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D012453:Saimiri
D001570:Benzodiazepinones; D015259:Dopamine Agents; D010078:Oxazines; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C042631:naxagolide; C058121:L 365260; D007980:Levodopa; D002766:Cholecystokinin; D020109:Devazepide; D002230:Carbidopa