Pharmacological Evaluation of the D2 and D3 Dopamine Receptor Selective Compounds on L-Dopa Dependent Abnormal Involuntary Movements in Rats

Kumar Rakesh, Pharmacological Evaluation of the D2 and D3 Dopamine Receptor Selective Compounds on L-dopa Dependent Abnormal Involuntary Movements in Rats. Master of Science (Pharmacology & Neuroscience), May 2008, 106 pp, 21 illustrations, references, 31 titles. Parkinson’s Disease (PD) is a progressive, neurodegenerative disease of the dopamine neurons that innervate the striatum and is characterized by resting tremor, rigidity, bardykinesia and postural instability. L-dopa treatment is the most common and effective therapy for PD. However, both motor (wear-off phenomena, rigidity and dyskinesia) and non-motor (sweating, tachycardia, restless leg syndrome, anxiety, depression, confusion, reduced alertness, psychosis and/or dementia) side effects are associated with long term L-dopa therapy. Motor complications depend on the duration of L-dopa treatment and the abnormal involuntary movements are known as L-dopa-induced dyskinesia (LID). Several studies have suggested a possible role of the dopamine D3 receptor subtype in LID. Here I evaluated the effects of various D2 and D3 dopamine receptor selective compounds on LID in 6-hydroxydopamine-induced complete lesioned hemi-parkinsonian model of rat. D3 dopamine receptor selective compounds (agonists, partial agonists or antagonists) have antidyskinetic effects on LID. Co-administration of D3 dopamine receptor agonist and D3 dopamine receptor antagonist has additive effects in attenuating the LID instead of antagonizing the effects of each other in vivo. D3 dopamine receptor selective compounds attenuated apomorphine-induced dyskinesia.