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  • Title: Effects of chronic treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content in rat brain: a possible implication of substance P in affective disorders.
    Author: Mitsushio H, Takashima M, Mataga N, Toru M.
    Journal: J Pharmacol Exp Ther; 1988 Jun; 245(3):982-9. PubMed ID: 2455042.
    Abstract:
    To assess the roles of substance P in neurologic or psychiatric illnesses, effects of acute or chronic (40- or 80-day dietary) treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content were investigated in the rat brain. Either acute or chronic trihexyphenidyl administration did not alter substance P content when administered alone and did not prevent the haloperidol-induced substance P decrease in the striatum and substantia nigra when coadministered with haloperidol. Chronic dietary carbamazepine administration dose-dependently increased substance P content in the striatum and substantia nigra, but not in the raphe area, in a haloperidol-reversible manner. Carbamazepine also dose-dependently increased gamma-aminobutyric acid levels in the substantia nigra without altering the striatal dopamine turnover rate. The lack of effect of trihexyphenidyl, an anticholinergic drug used to treat antipsychotic drug-induced extrapyramidal (Parkinson) syndromes, suggests that antipsychotic drug-induced reduction in substance P content is not involved in the extrapyramidal side effects. Since the effects of carbamazepine on substance P content are identical with previously described effects of lithium, an alteration in substance P neurotransmission may be one of the neurochemical bases of common clinical and behavioral effects of carbamazepine and lithium on affective disorders.
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