Chiba Hikari, Sato Haruka, Abe Kenji, Saito Toshiaki, Horiguchi Yoshie, Nojima Hiroshi, Taguchi Kyoji
Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, Koriyama, Japan.
Pharmacology. 2015;95(1-2):87-94. doi: 10.1159/000371580. Epub 2015 Jan 28.
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.
1,2,3,4-四氢异喹啉（TIQ）及其衍生物1-甲基-TIQ（1-MeTIQ）和1-苄基-TIQ（1-BnTIQ）内源性存在于人类大脑中。在本研究中，我们比较了TIQ衍生物对用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的大鼠黑质多巴胺能自发放电的影响。在低至中剂量范围（0.01-1 mg/kg），静脉注射MPTP可诱导放电频率短暂而显著增加。TIQ（0.01-30 mg/kg）无作用，1-MeTIQ和1-BnTIQ（0.01-10 mg/kg）静脉注射后立即引起较弱的放电频率增加。1-MeTIQ（80 mg/kg，腹腔注射）预处理可显著抑制高剂量MPTP诱导的多巴胺能自发放电减少。MPTP诱导的黑质硫代巴比妥酸反应性物质（TBARS）的产生也被1-MeTIQ预处理显著抑制。这些结果表明，与MPTP诱导的神经毒性相比，TIQ衍生物诱导的神经毒性相对较弱。1-MeTIQ对MPTP诱导毒性的神经保护作用可能部分归因于自由基的减少，如TBARS的减少所示。这种作用大概可防止细胞膜变性。
