1,2,3,4-Tetrahydro-2-methyl-4,6,7-isoquinolinetriol depletes catecholamines in rat brain.
1,2,3,4-Tetrahydro-2-methyl-4,6,7-isoquinolinetriol (TMIQ) was synthesised and tested for activity as a dopamine-depleting agent in rat brain. After intracerebroventricular infusion, TMIQ caused reductions in dopamine concentrations in substantia nigra, striatum, hypothalamus, and dorsal raphe, and reduction in noradrenaline concentrations in locus coeruleus. TMIQ also reduced 5-hydroxytryptamine concentrations in dorsal raphe and substantia nigra, although with a lower potency. Comparisons between TMIQ and MPTP showed that they were approximately equipotent in depleting dopamine in the substantia nigra, hypothalamus, and dorsal raphe. Pretreatment of animals with a combination of monoamine oxidase A and B inhibitors completely prevented the TMIQ-induced reductions in dopamine concentrations in substantia nigra and hypothalamus. Direct unilateral intrastriatal injections of TMIQ produced marked ipsilateral reductions in striatal dopamine, correlating with a behavioural response consisting of turning towards the side of injection. The results suggest that TMIQ should be evaluated further as a possible MPTP-like compound, which may derive from endogenous beta-hydroxylated catecholamines.
Liptrot
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Department of Anatomy, School of Medical Sciences, University of Bristol, England.
Holdup
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Phillipson
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D007839:Functional Laterality; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007263:Infusions, Parenteral; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D008845:Microinjections; D009638:Norepinephrine / Q000378:metabolism*; D009928:Organ Specificity; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
D007546:Isoquinolines; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C084360:1,2,3,4-tetrahydro-2-methyl-4,6,7-isoquinolinetriol; D003010:Clorgyline; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid