n-(4-(2-methoxyphenoxy)phenyl)-n-(2-2-2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine and Parkinsonian-Disorders

Antagonising serotonin (5-HT) type 2A receptors (5-HT. Five 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets exhibiting dyskinesia and psychosis-like behaviours (PLBs) were administered L-3,4-dihydroxyphenylalanine (L-DOPA) in combination with vehicle or the 5-HT. EMD-281,014 reduced dyskinesia and PLBs by up to 47% and 40%, respectively (both P < 0.001). The addition of LY-354,740, LY-487,379 and LY-354,740/LY-487,379 decreased dyskinesia by 56%, 65% and 77%, while PLBs were diminished by 55%, 63% and 71% (all P < 0.001). All treatment combinations provided anti-dyskinetic and anti-psychotic benefits significantly greater than those conferred by EMD-281,014 alone (all P < 0.05). The combination of EMD-281,014/LY-354,740/LY-487,379 resulted in anti-dyskinetic and anti-psychotic effects significantly greater than those conferred by EMD-281,014 with either LY-354,740 or LY-487,379 (both P < 0.05). No deleterious effects on L-DOPA anti-parkinsonian action were observed.. Our results suggest that combining 5-HT

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Antiparkinson Agents; Behavior, Animal; Bridged Bicyclo Compounds; Callithrix; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Indoles; Levodopa; Male; Parkinsonian Disorders; Piperazines; Psychotic Disorders; Pyridines; Receptors, Metabotropic Glutamate; Serotonin 5-HT2 Receptor Antagonists; Sulfonamides