Regional distribution of parkinsonism-preventing endogenous tetrahydroisoquinoline derivatives and an endogenous parkinsonism-preventing substance-synthesizing enzyme in monkey brain

Yamakawa, Toshio; Kotake, Yaichiro; Fujitani, Morioki; Shintani, Hideaki; Makino, Yasutaka; Ohta, Shigeru

doi:10.1016/s0304-3940(99)00786-7

Cited by 57 publications

(35 citation statements)

References 15 publications

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“…The cerebral concentration of 1MeTIQ in normal rat brains was recently determined as 3.5 ng/g tissue, exceeding several times (three- to fivefold) the concentrations of other simple tetrahydroisoquinolines (Inoue et al 2008). Most of the studies on 1MeTIQ were carried out on the brains of rodents, but the results on monkeys demonstrate that the regional distribution of 1MeTIQ, other simple tetrahydroisoquinolines, and 1MeTIQase activity are correlated (Yamakawa et al 1999). …”

Section: Synthesis Of 1metiq In the Brainmentioning

confidence: 99%

“…The tetrahydroisoquinoline family can be divided into compounds with catechol- and non-catechol structure. TIQ is the simplest representative of the group of non-catechol tetrahydroisoquinolines which occur naturally in plants and in a variety of food products (Makino et al 1988; Niwa et al 1989) as well as in the brain of humans, primates, and rodents (Kohno et al 1986; Makino et al 1988; Niwa et al 1987; Ohta et al 1987; Yamakawa et al 1999). …”

Section: Introductionmentioning

confidence: 99%

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1-Methyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Amine with Unexpected Mechanism of Action: New Vistas of Therapeutic Application

2013

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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.

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Section: Synthesis Of 1metiq In the Brainmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

1-Methyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Amine with Unexpected Mechanism of Action: New Vistas of Therapeutic Application

2013

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“…Using a gas chromatography/mass spectrometry method, Yamakawa et al (1999) observed relatively high levels of 1BnTIQ in the substantia nigra compared to other brain regions of normal monkeys. Acute 1BnTIQ administration induced parkinsonism in both rodents and monkeys (Kotake et al 1996;Abe et al 2001).…”

Section: Introductionmentioning

confidence: 95%

1-Benzyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Parkinsonism-Inducing Toxin, Strongly Potentiates MAO-Dependent Dopamine Oxidation and Impairs Dopamine Release: Ex vivo and In vivo Neurochemical Studies

2009

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1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is known to cause a parkinsonism-like syndrome in rodents and primates. In this study we evaluated the effects of single and multiple 1BnTIQ (50 mg/kg i.p.) administration on the concentrations of dopamine, serotonin, and respective metabolites (homovanillic acid, HVA; 3,4-dihydroxyphenylacetic acid, DOPAC; 3-methoxytyramine, 3-MT; and 5-hydroxyindolacetic acid, 5-HIAA), in substantia nigra, striatum (STR), and nucleus accumbens of Wistar rats. In addition, the effect of 1BnTIQ on locomotor activity and dopamine release in vivo was also estimated in rat STR. In a behavioral study, acute administration of 1BnTIQ (50 mg/kg i.p.) produced a significant decrease in exploratory locomotor activity. A high-performance liquid chromatography with electrochemical detection ex vivo study showed that a single injection of 1BnTIQ produced a dramatic fall in the dopamine concentration in the noted brain regions (approximately 65%; P < 0.01), but not in striatal serotonin. Moreover, 1BnTIQ reduced the content of the extraneuronal dopamine metabolite 3-MT by 70% (P < 0.01). Conversely, levels of DOPAC, HVA, and 5-HIAA were elevated by 220, 320, and 185%, respectively (P < 0.01). Interestingly, multiple 1BnTIQ treatments (50 mg/kg/day i.p. x 10 days) resulted in development of tolerance to its dopamine depressing effect, while the impairment of dopamine synthesis was persisted. An in vivo microdialysis study demonstrated that 1BnTIQ (50 mg/kg i.p.) produced a profound and long-lasting decrease in extraneuronal striatal dopamine. Concurrently, however, DOPAC and HVA were elevated. This comparison between ex vivo and in vivo effects of 1BnTIQ provides greater insight into the neurotoxic actions of 1BnTIQ specific to dopamine neurons. 1BnTIQ neurotoxicity may be related to an impairment of dopamine storage, leading to a fall in intraneuronal dopamine and enhanced dopamine catabolism through a monoamine oxidize-dependent oxidative pathway that results in free radical production and ultimate cell death. Because 1BnTIQ is an endogenous compound, it may be one of the factors responsible for idiopathic Parkinson's disease.

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“…Additionally, 1MeTIQ reversibly inhibited MAO A and B activities at micro-molar concentrations (Patsenka and Antkiewicz-Michaluk 2004) and showed the ability to inhibit free radical formation and to abolish H 2 O 2 generation from dopamine via the Fenton reaction (Antkiewicz-Michaluk et al 2006). 1MeTIQ which is present in the brain, is a mixture of (R)- and (S)-enantiomers enzymatically synthesized from 2-phenylethylamine and pyruvate by the 1MeTIQ-synthesizing enzyme, a membrane-bound protein localized in the mitochondrial synaptosomal fraction (Yamakawa and Ohta 1997; Yamakawa et al 1999). 1MeTIQ was shown to act as an anti-dopaminergic agent, but in contrast to typical neuroleptics, it did not induce catalepsy in animals (Antkiewicz-Michaluk et al 2000, 2014a).…”

Section: Introductionmentioning

confidence: 99%

Antidepressant-Like Effect of the Endogenous Neuroprotective Amine, 1MeTIQ in Clonidine-Induced Depression: Behavioral and Neurochemical Studies in Rats

et al. 2017

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Biogenic amines such as norepinephrine, dopamine, and serotonin play a well-described role in the treatment of mood disorders especially depression. Animal models are widely used to study antidepressant-like effect in rodents; however, it should be taken into account that pharmacological models do not always answer to the complexity of the disease processes. This study verified the behavioral (forced swim test (FST), locomotor activity test) and neurochemical effects (monoamines metabolism) of a low dose of clonidine (0.1 mg/kg i.p.) which was used as an experimental model of depression. In such pharmacological model, we investigated the antidepressant-like effect of an endogenous neuroprotective amine, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) administered in a dose of 25 mg/kg (i.p.) before clonidine in the behavioral and neurochemical tests carried out in rats. The behavioral study has shown that clonidine produced depression in the locomotor activity test but did not cause pro-depressive effect in the FST. 1MeTIQ produced antidepressant-like effect in the FST and completely antagonized clonidine-induced sedation in the locomotor activity test. Neurochemical data demonstrated that clonidine produced a significant inhibition of monoamine metabolism in the central nervous system. The release of dopamine, noradrenaline, and serotonin as well as the rate of their metabolism were diminished in the investigated brain structures (frontal cortex, hypothalamus, and striatum). 1MeTIQ completely antagonized the clonidine-induced depression of monoaminergic systems and restored their levels to the control values. 1MeTIQ as an endogenous neuroprotective compound with a distinct antidepressant-like activity in rodents produces hope on the efficiency of antidepressant medicines for future practical clinical use.

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Regional distribution of parkinsonism-preventing endogenous tetrahydroisoquinoline derivatives and an endogenous parkinsonism-preventing substance-synthesizing enzyme in monkey brain

Cited by 57 publications

References 15 publications

1-Methyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Amine with Unexpected Mechanism of Action: New Vistas of Therapeutic Application

1-Methyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Amine with Unexpected Mechanism of Action: New Vistas of Therapeutic Application

1-Benzyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Parkinsonism-Inducing Toxin, Strongly Potentiates MAO-Dependent Dopamine Oxidation and Impairs Dopamine Release: Ex vivo and In vivo Neurochemical Studies

Antidepressant-Like Effect of the Endogenous Neuroprotective Amine, 1MeTIQ in Clonidine-Induced Depression: Behavioral and Neurochemical Studies in Rats

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