title: 1-Methyl-1,2,3,4-tetrahydroisoquinoline, an endogenous amine with unexpected mechanism of action: new vistas of therapeutic application.
abstract: This review outlines the effects of 1,2,3,4-tetrahydroisoquinoline (TIQ) and its derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), endogenous substances imbued with high pharmacological potential and broad spectrum of action in brain. 1MeTIQ has gained special interest as a neuroprotectant, and its ability to antagonize the behavioral syndrome produced by well-known neurotoxins (e.g., MPTP; rotenone). This review is thus focused on mechanisms of action of 1MeTIQ in behavioral, neurochemical, and molecular studies in rodents; also, effects of TIQ and 1MeTIQ on dopamine metabolism; and neuroprotective properties of TIQ and 1MeTIQ in vitro and in vivo. Finally, antiaddictive properties of 1MeTIQ will be described in cocaine self-administered rats. Findings implicate TIQ and especially its methyl derivative 1MeTIQ in unique and complex mechanisms of neuroprotection in various neurodegenerative illnesses of the central nervous system. We believe that MAO inhibition, free radicals scavenging properties, and antagonism to the glutamatergic system may play an essential role in neuroprotection. In addition, the results strongly support the view that 1MeTIQ has a considerable potential as a drug for combating substance abuse, through the attenuation of craving.
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, Smetna Str.12, 31-343, Kraków, Poland, antkiew@if-pan.krakow.pl.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wąsik
authors.forename: Jerzy
authors.initials: J
authors.lastname: Michaluk
mesh_terms: D000588:Amines / Q000627:therapeutic use; D000818:Animals; D001923:Brain Chemistry; D019970:Cocaine-Related Disorders / Q000188:drug therapy; D018492:Dopamine Antagonists / Q000627:therapeutic use*; D006801:Humans; D009021:Morphine Dependence / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*
chemical_list: D000588:Amines; D018492:Dopamine Antagonists; D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; C014843:1,2,3,4-tetrahydroisoquinoline