Effects of sarizotan on the corticostriatal glutamate pathways.
The effects of sarizotan, a 5-HT(1A) agonist with additional affinity for D(3) and D(4) receptors, have been studied on the corticostriatal glutamate pathways using dual-probe microdialysis in the awake rat. Sarizotan given systemically (0.1-10 mg/kg s.c.) or perfused into the motor cortex (10 microM) produced 20-30% reduction of cortical and striatal glutamate levels. The inhibitory effects of the systemic sarizotan on cortical and striatal glutamate levels were counteracted by intracortical perfusion with the 5-HT(1A) antagonist WAY100135 (10 microM). These findings suggest that the anti-dyskinetic properties of sarizotan could be mediated via its 5-HT(1A) agonist actions in the motor cortex, leading to reduced activity in the corticostriatal glutamate pathways with reduced activation of the striatopallidal GABA pathway mediating motor inhibition.
Antonelli
Tiziana
T
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, Italy.
Fuxe
Kjell
K
Tomasini
Maria C
MC
Bartoszyk
Gerd D
GD
Seyfried
Christoph A
CA
Tanganelli
Sergio
S
Ferraro
Luca
L
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D020820:Dyskinesias / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009044:Motor Cortex / Q000187:drug effects* / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism; D009930:Organic Chemicals / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D000978:Antiparkinson Agents; D009930:Organic Chemicals; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C081293:WAY 100135; D012701:Serotonin; D018698:Glutamic Acid; C443959:sarizotan