title: A possible physiological role for cerebral tetrahydroisoquinolines.
abstract: Tetrahydroisoquinolines present in the mammalian brain, 1,2,3,4-tetrahydroisoquinoline (TIQ) and salsolinol, suspected to cause neurodegeneration leading to Parkinson's disease, were investigated to find their possible physiological role. To this aim their behavioral and receptor effects induced after a single dose were tested in mice and rats. Both compounds do not affect significantly the basal locomotor activity, very effectively block hyperactivity induced by apomorphine (rats) and amphetamine (mice), only partially block hyperactivity induced by scopolamine, do not affect locomotor stimulation induced by cocaine, and strongly augment the running fit induced by morphine (mice). They do not produce extrapyramidal symptoms and do not potentiate haloperidol-induced catalepsy (rats). TIQ and salsolinol do not displace antagonists of several receptors (including D(1) and D(2)) from their binding sites, but displace the agonists of Alpha(2)-adrenoceptors, [(3)H]clonidine and of dopamine receptors, [(3)H]apomorphine. The results indicate that salsolinol and TIQ act as specific antagonists of agonistic conformation of dopamine receptors, and owing to that may play a role of endogenous feed-back regulators of the dopaminergic system. Those properties make tetrahydroisoquinolines potential antidopaminergic drugs devoid of extrapyramidal effects, with possible application in substance addiction disorder as anti-craving agents.
authors.affiliation: Institute of Pharmacology, P.A.N., Smetna 12, 31-343 Kraków, Poland. nfvetula@cyf-kr.edu.pl
authors.forename: Jerzy
authors.initials: J
authors.lastname: Vetulani
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
authors.forename: Irena
authors.initials: I
authors.lastname: Nalepa
authors.forename: Mario
authors.initials: M
authors.lastname: Sansone
mesh_terms: D000818:Animals; D001480:Basal Ganglia Diseases / Q000378:metabolism / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology; D008568:Memory / Q000502:physiology; D009068:Movement / Q000502:physiology; D017072:Neostriatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology; D010766:Phosphorylation; D018091:Receptors, AMPA / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid