GABA receptor agonists and extrapyramidal motor function: therapeutic implications for Parkinson's disease.
GABA receptor agonists display a dual action on DA-mediated events. One includes a decrease in DA release, reduction in DA receptor density, and decreased response of postsynaptic cells to dopaminergic stimulation; it results in antidopaminergic effects. The other consists of a reduction of striatal cholinergic activity resulting in a facilitation of dopaminergic effects. These two effects could be dissociated depending on the dose of GABA receptor agonists. This dual action probably explains the results of clinical trials showing either amelioration of parkinsonian symptoms with aggravation of L-DOPA-induced dyskinesia or improvement of dyskinesia without or with aggravation of parkinsonian symptoms.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002799:Cholinergic Fibers / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005116:Extrapyramidal Tracts / Q000187:drug effects*; D006801:Humans; D009048:Motor Skills / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000978:Antiparkinson Agents; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; C017985:progabide; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D004298:Dopamine