title: Effects of 1,2,3,4-tetrahydroisoquinoline derivatives on dopaminergic spontaneous discharge in substantia nigra neurons in rats.
abstract: 1,2,3,4-Tetrahydroisoquinoline (TIQ) and its derivatives, 1-methyl-TIQ (1-MeTIQ) and 1-benzyl-TIQ (1-BnTIQ), are endogenously present in the human brain. In this study, we compared the effects of TIQ derivatives on spontaneous nigral dopaminergic discharge in rats treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the low-to-middle dose range (0.01-1 mg/kg), intravenous administration of MPTP induced a transient and potent increase in the firing rate. TIQ (0.01-30 mg/kg) had no effects, and 1-MeTIQ and 1-BnTIQ (0.01-10 mg/kg) produced a weaker increase in the firing frequency immediately after intravenous administration. Pretreatment with 1-MeTIQ (80 mg/kg, i.p.) significantly inhibited the decrease in dopaminergic spontaneous firing induced by a high dose of MPTP. The nigral induction of thiobarbituric acid-reactive substances (TBARS) by MPTP was also significantly suppressed by pretreatment with 1-MeTIQ. These results suggest that the neurotoxicity induced by TIQ derivatives is relatively weak compared to that induced by MPTP. The neuroprotective effect of 1-MeTIQ from MPTP-induced toxicity may be partially due to a decrease in free radicals, as suggested by a decrease in TBARS. This action presumably prevents cell membrane degeneration.
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, Koriyama, Japan.
authors: Hikari
authors: H
authors: Chiba
authors: Haruka
authors: H
authors: Sato
authors: Kenji
authors: K
authors: Abe
authors: Toshiaki
authors: T
authors: Saito
authors: Yoshie
authors: Y
authors: Horiguchi
authors: Hiroshi
authors: H
authors: Nojima
authors: Kyoji
authors: K
authors: Taguchi
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D009498:Neurotoxins; D044005:Tetrahydroisoquinolines; D017392:Thiobarbituric Acid Reactive Substances; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine