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Effect of haloperidol and its metabolites on dopamine and noradrenaline uptake in rat brain slices

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Abstract

The effects of haloperidol and its metabolites on dopamine (DA) and noradrenaline (NA) uptake were investigated. Both direct uptake of [3H]DA and [3H]NA into the rat striatal and hippocampus slices and binding of a specific DA uptake inhibitor [3H]GBR-12935 were employed in the present study. Haloperidol pyridinium (HP+), haloperidol 1,2,3,6-tetrahydropyridine (HTP), 4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine (CPTP) and reduced haloperidol (RHAL) are potent inhibitors of DA uptake. HTPN-oxide (HTPNO) exhibits a relatively weak effect on DA uptake. Other metabolites of haloperidol, i.e. 4-(4-chlorophenyl)-4-hydroxypyridine (CPHP) and haloperidolN-oxide (HNO), as well as haloperidol itself possess negligible inhibitory effect on DA uptake. HP+ has been shown to be an amine releaser. It is possible that HP+ may induce amphetamine-like neurotoxicity. The effects of the metabolites of haloperidol on [3H]NA uptake are similar to those on [3H]DA uptake. HP+ appears to be different from MPP+, which is a more potent [3H]NA uptake blocker than on [3H]DA uptake. Although haloperidol exhibits no DA uptake inhibitory effect, it has a high affinity for the [3H]GBR-12935 binding site. The possible pharmacological implications such inhibitory effects on amine uptake are discussed.

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  1. Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, S7N 5E4, Saskatoon, Saskatchewan, Canada

    J. Fang & P. H. Yu

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  1. J. Fang
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  2. P. H. Yu
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Fang, J., Yu, P.H. Effect of haloperidol and its metabolites on dopamine and noradrenaline uptake in rat brain slices. Psychopharmacology 121, 379–384 (1995). https://doi.org/10.1007/BF02246078

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  • DOI: https://doi.org/10.1007/BF02246078

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