RESUMO
The neuropeptide melanocyte-inhibiting factor (MIF) or L-propyl-L-leucyl-glycinamide (PLG) has been reported in some studies to improve the motor signs of Parkinson's disease (PD) and in rodent models of PD. In this study of oral and intravenous MIF in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets, a wide range of doses of MIF administered alone (0.25, 1, 2, 5, 10, 20 mg/kg orally) did not increase locomotor activity, relieve motor disability, or induce dyskinesias. When MIF (1.0 and 5.0 mg/kg orally or 10 and 20 mg/kg intravenously) was administered concomitantly with levodopa/benserazide, no significant differences in motor function or dyskinesias were observed compared with levodopa/benserazide alone. The results of this first study of MIF in the marmoset MPTP model provide no encouragement for the reinvestigation of MIF in the clinical management of the motor signs of PD.
Assuntos
Antiparkinsonianos/administração & dosagem , Hormônio Inibidor da Liberação de MSH/administração & dosagem , Transtornos Parkinsonianos/tratamento farmacológico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Administração Oral , Animais , Antiparkinsonianos/toxicidade , Benserazida/administração & dosagem , Benserazida/toxicidade , Callithrix , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Infusões Intravenosas , Levodopa/administração & dosagem , Levodopa/toxicidade , Locomoção/efeitos dos fármacos , Hormônio Inibidor da Liberação de MSH/toxicidade , Masculino , Atividade Motora/efeitos dos fármacosRESUMO
With the use of the method Chick Embryotoxicity Screening Test II (CHEST II), the potential neuropeptides L-prolyl-L-leucyl-glycinamide (MIF), cyclo(1-aminocyclo-pentanecarbonyl-L-alanyl)[cyclo(Acp-Ala)] and cyclo(glycyl-L-leucyl)[Cyclo(Gly-Leu)] were tested in the critical developmental periods of d 1.5 to 4 of chick embryogenesis in order to objectively examine their undesirable interactions with the developing morphogenetic systems of the brain, eye, face, body wall, limbs, trunk and heart. All compounds tested showed positive dose- and stage-response relationships. The body wall defects are the prevailing type of malformations.