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A possible physiological role for cerebral tetrahydroisoquinolines

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Abstract

Tetrahydroisoquinolines present in the mammalian brain, 1,2,3,4-tetrahydroisoquinoline (TIQ) and salsolinol, suspected to cause neurodegeneration leading to Parkinson's disease, were investigated to find their possible physiological role. To this aim their behavioral and receptor effects induced after a single dose were tested in mice and rats. Both compounds do not affect significantly the basal locomotor activity, very effectively block hyperactivity induced by apomorphine (rats) and amphetamine (mice), only partially block hyperactivity induced by scopolamine, do not affect locomotor stimulation induced by cocaine, and strongly augment the running fit induced by morphine (mice). They do not produce extrapyramidal symptoms and do not potentiate haloperidol-induced catalepsy (rats). TIQ and salsolinol do not displace antagonists of several receptors (including D1 and D2) from their binding sites, but displace the agonists of α2-adrenoreceptors, [3H] clonidine and of dopamine receptors, [3H] apomorphine. The results indicate that salsolinol and TIQ act as specific antagonists of agonistic conformation of dopamine receptors, and owing to that may play a role of endogenous feed-back regulators of the dopaminergic system. Those properties make tetrahydroisoquinolines potential antidopaminergic drugs devoid of extrapyramidal effects, with possible application in substance addiction disorder as anti-craving agents.

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Authors and Affiliations

  1. Institute of Pharmacology, P.A.N., Smetna 12.31-343, Kraków, Poland

    Jerzy Vetulani, Lucyna Antkiewicz-Michaluk & Irena Nalepa

  2. Istituto di Psicobiologia e Psicofarmacologia, C.N.R., Roma, Italy

    Mario Sansone

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  1. Jerzy Vetulani
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  2. Lucyna Antkiewicz-Michaluk
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  3. Irena Nalepa
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  4. Mario Sansone
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Correspondence to Jerzy Vetulani.

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Vetulani, J., Antkiewicz-Michaluk, L., Nalepa, I. et al. A possible physiological role for cerebral tetrahydroisoquinolines. neurotox res 5, 147–155 (2003). https://doi.org/10.1007/BF03033379

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  • DOI: https://doi.org/10.1007/BF03033379

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