Clozapine reduces L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesias in parkinsonian patients. To test if the antidyskinetic effect of clozapine is related to antagonism at the dopamine D(4) receptor, we investigated the effect of 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1, 4]benzodiazepine (JL-18), a structural analog of clozapine which is more selective for this receptor. Four 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa were used in this study. They were injected subcutaneously (s.c.) with L-Dopa methyl ester (125 mg per animal) plus benserazide (50 mg per animal; L-Dopa/benserazide) alone or in combination with JL-18 (at the doses of 0.1, 0.3, or 0.9 mg/kg, s.c.). Subcutaneous injection of sterile saline was used as control. L-Dopa/benserazide increased locomotion and improved parkinsonism but also induced dyskinesias. Co-administration of JL-18, at low doses (0.1, 0.3 mg/kg) with L-Dopa/benserazide, produced a dose-dependent reduction in L-Dopa-induced dyskinesias without a parallel return to parkinsonism. The present results suggest that novel selective dopamine D(4) receptor antagonists may represent a useful tool to reduce L-Dopa-induced dyskinesias.
Clozapine reduces L-3,4-dihydroxyphenylalanine ( L - Dopa)-induced dyskinesias in parkinsonian patients . To test if the antidyskinetic effect of clozapine is related to antagonism at the dopamine D(4 ) receptor , we investigated the effect of 8-methyl-6-(4-methyl-1-piperazinyl)-11H - pyrido[2,3-b][1 , 4]benzodiazepine ( JL-18 ) , a structural analog of clozapine which is more selective for this receptor . Four 1-methyl-4-phenyl-1,2,3 , 6-tetrahydropyridine ( MPTP)-treated cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias to L - Dopa were used in this study . They were injected subcutaneously ( s.c . ) with L - Dopa methyl ester ( 125 mg per animal ) plus benserazide ( 50 mg per animal ; L - Dopa / benserazide ) alone or in combination with JL-18 ( at the doses of 0.1 , 0.3 , or 0.9 mg / kg , s.c . ) . Subcutaneous injection of sterile saline was used as control . L - Dopa / benserazide increased locomotion and improved parkinsonism but also induced dyskinesias . Co - administration of JL-18 , at low doses ( 0.1 , 0.3 mg / kg ) with L - Dopa / benserazide , produced a dose - dependent reduction in L - Dopa - induced dyskinesias without a parallel return to parkinsonism . The present results suggest that novel selective dopamine D(4 ) receptor antagonists may represent a useful tool to reduce L - Dopa - induced dyskinesias .
Which drug is benserazide usually co-administered with?
Which drug is benserazide usually co - administered with ?
L-Dopa
L-Dopa