Dipeptide analog of neurotensin active site prevents the development of experimental Parkinson's syndrome in mice.
Chronic administration of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) to C57BL/6 mice caused death of all animals within 7 days. Dipeptide analog of neurotensin active site injected with this neurotoxin protected the mice from death even after 2-week intoxication. When younger mice and lower dose of neurotoxin (25 mg/kg) were used, all animals survived, but after 2 weeks they developed parkinsonian syndrome with muscular rigidity, akinesia, decrease in motor and explorative activities. In mice treated with dipeptide analog of neurotensin active site these manifestations of oligokinesia caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were less pronounced and the corresponding parameters approximated the control values. Possible mechanisms of neuroprotective action of neurotensin active site analog are discussed.
Lutsenko
V K
VK
State Research Institute of General Pathology and Pathological Physiology; State Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow. lutsenko@go.ru
Vukolova
M N
MN
Kucheryanu
V G
VG
Gudasheva
T A
TA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects; D015259:Dopamine Agents / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009496:Neurotensin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D013574:Synaptosomes / Q000187:drug effects; D013997:Time Factors
D015259:Dopamine Agents; D009498:Neurotoxins; D009496:Neurotensin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine