1‐Methyl‐ 1,2,3,4‐Tetrahydroisoquinoline, Decreasing in 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine‐Treated Mouse, Prevents Parkinsonism‐Like Behavior Abnormalities

Abstract

In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse brain, there was no significant increase or decrease in the content of an endogenous amine, 1,2,3,4-tetrahydroisoquinoline (TIQ), which is well noted for inducing parkinsonism, whereas another endogenous amine, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ), was markedly reduced. This result agrees with the finding in human idiopathic parkinsonianism, confirmed by our previous research. In addition, pretreatment with 1-MeTIQ completely prevented MPTP- or TIQ-inducing bradykinesia, a symptom of parkinsonism. This study confirmed that 1-MeTIQ plays an important role in preventing the pathogenesis of parkinsonism and is a possible leading compound of anti-parkinsonism agents.

Novel Endogenous 1,2,3,4‐Tetrahydroisoquinoline Derivatives: Uptake by Dopamine Transporter and Activity to Induce Parkinsonism

“…Many TIQ derivatives have been found in animals, including humans, as endogenous amines (Sjoquist and Ljungquist, 1985;Kohno et al, 1986;Kotake et al, 1,995;Nakagawa et al, 1996), and some of them may be related to the pathogenesis of parkinsonism or Parkinson's disease (Ohta et al, 1987;Nagatsu and Yoshida, 1988;Tasaki et al, 1991;Maruyama et al, 1993;Kotake et al, 1995Kotake et al, , 1996. We report here that 3 ',4 'DHBnTIQ and 6,7DHBnTIQ also exist in mouse brain as endogenous parkinsonism-related TIQ derivatives.…”

“…TIQ and 1-benzyl-1 ,2,3,4-tetrahydroisoquinoline (1BnTIQ) could induce parkinsonism in rodents (Tasaki et al, 1991;Kotake et al, 1995) and a primate (Kotake et al, 1996), and 1BnTIQ existed in CSF of parkinsonian patients at about three times higher levels than in disease controls (Kotake et al, 1995). Thus, TIQ and 1BnTIQ are plausible candidates as Parkinson's disease-inducing substances, but we speculated that other neurotoxins might also be present in the CNS.…”

Synthesis and Neurotoxicity of Tetrahydroisoquinoline Derivatives for Studying Parkinson's Disease

“…21) 1-Methyl-TIQ is present in human, rat and mouse brains 17,22,24,55) as a mixture of (R)-and (S)-enantiomers. Its concentration decreases in the parkinsonian brain 56) and during aging, especially in the substantia nigra and striatum, which are implicated in PD.…”

“…24) 1-Methyl-TIQ prevents MPTP-, TIQ-and 1-benzyl-TIQ-induced behavioral abnormalities, 19,24) and it is the only endogenous parkinsonism-preventing agent discovered to date. The inhibitory effect on mitochondrial respiration rate induced by MPP ϩ that was seen in rat liver mitochondria and striatal synaptosomes was prevented by 1-methyl-TIQ.…”

“…[18][19][20][21] TIQ derivatives (TIQs) have also been found in the brain of other animal species, 19,22,23) and can induce parkinsonism in primates and rodents. 24,25) TIQ is commonly found in a variety of foods (e.g. milk, cocoa and bananas) 26,27) and it easily penetrates the blood-brain barrier.…”