Dopaminomimetic action of diphenylhydantoin in rat striatum: Effect on homovanillic acid and cyclic AMP levels

Abstract

Diphenylhydantoin (DPH) is known to induce reversible paroxysmal dyskinesias and paranoid psychosis in humans, but its interactions with dopamine (DA) metabolism are not clear. Single doses of DPH (60-100 mg kg-1), with serum levels over 10 micrograms ml-1, reduced homovanillic acid (HVA) levels in rat striatum. The DPH-induced HVA decrease was enhanced by supersensitivity of postsynaptic DA receptors following chronic haloperidol (Hal) administration. DPH 60 mg kg-1 given acutely enhanced the HVA decrease induced by apomorphine (Apo) and partially counteracted the HVA increase following acute Hal (0.1-0.5-2 mg kg-1). After chronic DPH treatment, Apo was ineffective in reducing striatal HVA levels. Concomitant chronic treatment with DPH and Hal counteracted the development of supersensitivity of postsynaptic DA receptors to Apo. Single doses of DPH (30-60-100 mg kg-1) increased cyclic AMP striatal content; this effect was blocked by Hal. A dopaminomimetic DPH action and a subsensitivity of postsynaptic DA receptors after chronic DPH seem to be suggested. These effects could be related to the dyskinetic and psychotic syndromes produced by the drug.

The role of dopamine in epilepsy

“…Carbamazepine has a presynaptic dopaminereleasing action, both in vitro (Barros et al, 1986) and in vivo (Kaneko et al, 1993), which may well be a component of its anticonvulsant mechanism. Phenytoin leads to dopaminergic supersensitivity after long-term administration to rats (Lalonde, 1985; but see Lepore et al, 1985) and to dopamine-like orofacial dyskinesias in epileptic patients. Likewise, vigabatrin treatment of epilepsy has been sporadically linked to psychosis, with evidence of increased HVA levels in the CSF following acute (Ben-Menachem et al, 1989) but not chronic (Riekkinen et al, 1989) vigabatrin treatment and of increased *231-IBZM binding to Dz receptors in the basal ganglia of the left hemisphere of six chronic epileptics (Ring et al, 1992).…”

Homovanillic Acid and Prolactin in Plasma and CSF of Medicated Epileptic Patients

“…creasing, if any, effect on DA turnover. Although some authors (Lepore et al, 1985) reported a dopaminomimetic action of phenytoin and a subsensitivity of DA receptors after chronic administration of the drug, others (Lalonde, 1985) proposed a dopaminergic supersensitivity as a result of a long-term phenytoin administration.…”