Effect of Melperone, Two of its Metabolites and Thiothixene on Central Monoamine Metabolism and Prolactin Levels in Rodents

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Abstract
The effects of melperone and thiothixene on the concentrations of monoamine metabolites in brain and prolactin in the serum of rats and mice were determined. Both drugs increased brain concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in a dosedependent manner. 5‐Hydroxyindoleacetic acid (5‐HIAA) was unaffected. The effect of thiothixene was longer lasting and about 5 times greater than that of melperone. Melperone, but not thiothixene, increased levels of 3‐methoxy‐4‐hydroxyphenylethylene glycol (MOPEG). Several hours after administration of melperone, levels of HVA and MOPEG were diminished.Both drugs increased prolactin concentrations in rat serum. Thiothixene was about 10 times more potent than melperone.Of two urinary metabolites of melperone investigated, one caused the same qualitative effects on monoamine metabolism as melperone itself but with reduced potency. The other metabolite was ineffective.