EFFECT OF TRIHEXYPHENIDYL, A NONSELECTIVE ANTIMUSCARINIC DRUG, ON DECARBOXYLATION OF L-DOPA IN HEMI-PARKINSON RATS

in vivo microdialysis was used to study the effect of the non-selectiv e muscarinic antagonist, trihexyphenidyl, on the decarboxylation of le vodopa (L-dopa) in the striatum of hemi-Parkinson rats, in normal rats , continuous perfusion of trihexyphenidyl (1 mM) via the microdialysis probe induced a significant increase in striatal dopamine release, fo llowed by a decrease to below baseline values. A similar effect was ob served, though less pronounced, in denervated striatum of rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. In t hese hemi-Parkinson rats, continuous striatal perfusion of trihexyphen idyl had no effect on the biotransformation of locally applied L-dopa (2 mu M for 20 min) to dopamine in either intact or denervated striatu m. However, systemic administration of trihexyphenidyl (1.5 mg/kg i.p. ) produced an attenuation of the L-dopa-induced dopamine release in th e intact striatum (contralateral to the lesion) of hemi-Parkinson rats . This effect was absent in the denervated striatum of these animals. We confirmed that L-dopa induces an increase in striatal dopamine outp ut which is influenced by the severity of the dopaminergic denervation . The absence of an effect of trihexyphenidyl locally applied in the s triatum, on biotransformation of L-dopa suggests that the site of acti on of antimuscarinic drugs may not be in the striatum and, therefore, remains unclear. The mechanism of action of these drugs is not well un derstood but appears more complicated than previously thought. (C) 199 8 Elsevier Science B.V. All rights reserved.