title: Acute, sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): a novel drug bioavailability enhancer.
abstract: An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.
authors.affiliation: PK-PD Toxicology Division, Indian Institute of Integrative Medicine, CSIR, Jammu 180001, India.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Rayees
authors.forename: Rohit
authors.initials: R
authors.lastname: Sharma
authors.forename: Gurdarshan
authors.initials: G
authors.lastname: Singh
authors.forename: Ishtiyaq Ahmad
authors.initials: IA
authors.lastname: Najar
authors.forename: Amarinder
authors.initials: A
authors.lastname: Singh
authors.forename: Dastagir Basheer
authors.initials: DB
authors.lastname: Ahamad
authors.forename: Subash Chander
authors.initials: SC
authors.lastname: Sharma
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Tikoo
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Gupta
authors.forename: Payare Lal
authors.initials: PL
authors.lastname: Sangwan
authors.forename: Surjeet
authors.initials: S
authors.lastname: Singh
authors.forename: Surinder
authors.initials: S
authors.lastname: Koul
authors.forename: Rakesh Kamal
authors.initials: RK
authors.lastname: Johri
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology*; D001769:Blood / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005260:Female; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D023382:Toxicity Tests, Acute; D059551:Toxicity Tests, Subacute; D016482:Urinalysis
chemical_list: C583244:5-(3,4-methylenedioxyphenyl)-4-ethyl-2,4-pentadienoic acid piperidide; D000700:Analgesics; D000927:Anticonvulsants; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D010424:Pentobarbital