Pharmacological assessments of potent A2Areceptor antagonist IDPU (1-(7-imino-3-propyl-2,3-dihydrothiazolo[4,5-d]pyrimidin-6(7H)-yl)urea) in rodent model of haloperidol induced Parkinson like symptoms.
A2Areceptor antagonists emerged as potential candidate for management of Parkinson's disease. Earlier we had reported the therapeutic potential of 1-(7-imino-3-propyl-2,3-dihydrothiazolo[4,5-d]pyrimidin-6(7H)-yl) urea (IDPU) as A2Areceptor antagonist. Herein, we have investigated the effect of IDPU in attenuation of haloperidol induced Parkinson like symptoms in rats. It has successfully restored hypo-locomotion induced by haloperidol and NECA. IDPU also displayed protective effect against oxidative stress induced by chronic haloperidol treatment in rats. The antidepressant activity of IDPU was determined in mice showed that it imperatively reduced depression like symptoms in well-established depression models viz. TST and FST. Additionally, IDPU was found to be a safe and non-toxic chemical entity in acute, sub-acute and neurotoxicity studies. In silico study of IDPU showed acceptable physicochemical parameters and in vitro screening exhibited satisfactory metabolic stability. This study clearly indicates that A2Areceptor antagonist IDPU is able to ameliorate Parkinsonian symptoms without exerting any significant toxicity.
Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi, India.
Namrata
N
Kumari
Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi, India.
Saurabh
S
Agrawal
Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi, India. Electronic address: pmlsci@yahoo.com.
Pratibha Mehta
PM
Luthra
D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use* / Q000633:toxicity; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use* / Q000633:toxicity; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006220:Haloperidol; D008297:Male; D051379:Mice; D009043:Motor Activity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013844:Thiazoles / Q000627:therapeutic use* / Q000633:toxicity; D023382:Toxicity Tests, Acute; D059551:Toxicity Tests, Subacute; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity
C000623094:(1-(7-imino-3-propyl-2,3-dihydrothiazolo(4,5-d)pyrimidin-6(7H)-yl)urea; D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D043705:Receptor, Adenosine A2A; D013844:Thiazoles; D019830:Adenosine-5'-(N-ethylcarboxamide); D014508:Urea; D006220:Haloperidol
A(2A) receptor antagonist; Catalepsy; Depression; IDPU; Oxidative stress; Toxicity