title: Preladenant, a novel adenosine A(2A) receptor antagonist for the potential treatment of parkinsonism and other disorders.
abstract: Adenosine A(2A) receptor antagonists exert antiparkinsonian effects in animal models and several drugs in this class are currently being assessed in clinical trials. Preladenant (SCH-420814) is an adenosine A(2A) receptor antagonist with a high affinity and very high selectivity for adenosine A(2A) receptors, which is being developed by Merck & Co Inc (following its acquisition of Schering-Plough Corp) for the potential treatment of Parkinson's disease. Preclinical studies in rodent and primate models of parkinsonism demonstrated that preladenant can reverse the motor impairments induced by dopamine depletion or antagonism. Phase I and II clinical trials indicated that preladenant was well tolerated. Moreover, preladenant met its major endpoints by reducing OFF time and increasing ON time in l-DOPA-treated patients with Parkinson's disease, without worsening dyskinesias. Therefore, preladenant may have considerable utility for the treatment of Parkinson's disease, as well as the parkinsonian side effects of dopamine D2 receptor antagonists. As research has suggested that adenosine A(2A) receptor antagonists are active in animal models of effort-based decision making, it is possible that preladenant could also be useful for treating energy-related symptoms, such as fatigue, psychomotor retardation and anergia in patients with parkinsonism or depression. At the time of publication, phase III clinical trials were recruiting patients with Parkinson's disease.
authors.affiliation: University of Connecticut, Behavioral Neuroscience Division, Department of Psychology, 406 Babbidge Road, Unit 1020, Storrs, CT 06269-1020, USA. john.salamone@uconn.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D011743:Pyrimidines / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D014230:Triazoles / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D014230:Triazoles; C539997:2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine