title: Neuroprotective Effect of the Endogenous Amine 1MeTIQ in an Animal Model of Parkinson's Disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder that is hallmarked by pathological changes associated with the death of dopaminergic neurons, particularly in the extrapyramidal system (substantia nigra pars compacta, striatum) of the brain. Although the causes of slow neuronal death in PD are unknown, both genetic and environmental factors are likely involved. Endogenous isoquinolines, such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), present in the human brain have been previously reported to participate in the pathogenesis of PD. The chronic administration of 1BnTIQ induced parkinsonism in primates, and this effect might be associated with idiopathic PD. However, another endogenous derivative of tetrahydroisoquinoline, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), displays clear neuroprotective properties in the brain. In the present study, we investigated the neuroprotective effects of 1MeTIQ (25 and 50 mg/kg) in an animal model of PD after the chronic administration of 1BnTIQ (25 mg/kg). Behavioral analyses demonstrate that both acute and repeated treatment with 1MeTIQ completely antagonized 1BnTIQ-induced changes in rat locomotor activity. Neurochemical experiments indicate that 1MeTIQ co-administered with 1BnTIQ completely antagonized 1BnTIQ-induced reduction in the dopamine (DA) concentration in rat brain structures. In conclusion, the results demonstrate that 1MeTIQ possesses important neuroprotective properties in the animal model of PD and that the rats did not develop tolerance after its chronic administration.
authors: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland. wasik@if-pan.krakow.pl.
authors: Agnieszka
authors: A
authors: Wąsik
authors: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland.
authors: Irena
authors: I
authors: Romańska
authors: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland.
authors: Jerzy
authors: J
authors: Michaluk
authors: Department of Biochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland.
authors: Agnieszka
authors: A
authors: Zelek-Molik
authors: Department of Biochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland.
authors: Irena
authors: I
authors: Nalepa
authors: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland.
authors: Lucyna
authors: L
authors: Antkiewicz-Michaluk
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010300:Parkinson Disease; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage* / Q000633:toxicity*
chemical_list: D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; D004298:Dopamine; C084924:1,2,3,4-tetrahydro-1-(phenylmethyl)isoquinoline
keywords: 1-benzyl-1,2,3,4-tetrahydroisoquinoline; 1-methyl-12,3,4-tetrahydroisoquinoline; Dopamine metabolism; Parkinson’s disease