title: Investigation of piperidine derivatives in ex vivo models of pain and platelet aggregation.
abstract: Piperidine derivatives are known to exhibit analgesic activities and are likely to possess the ability to block the effects of prostaglandins through inhibition of downstream signaling pathways. The present study investigated the activity of five derivatives (PD2-6) of 4-(4'-bromophenyl)-4-piperidinol (PD1), against pain and platelet aggregation mediated by the release of prostaglandins and thromboxane A2, respectively. The results showed that compound PD1 and its two phenacyl derivatives PD3 and PD5 exhibited a highly significant analgesic effect (p < 0.01), whereas PD4 and PD6 also showed significant activity. PD3, the most active analgesic compound when docked to the opioid receptor, had interactions between the oxygen of its nitro group and the amino group of ARG 573, indicating a distance of 1.2563 Å. The antiplatelet data showed that compound PD5 (4-(4'-bromo-phenyl)-4-hydroxy-1-[2-(2″,4″-dimethoxyphenyl)-2-oxo-ethyl]-piperidinium bromide) had an IC(50) = 0.06 mM, which was the most active compound, whereas PD3 was the second most active compound against platelet aggregating factor-induced aggregation with an IC(50) = 80 mM. Acetyl salicylic acid (IC(50) = 150 μM) was used as a positive control.
authors.affiliation: HEJ Research Institute of Chemistry, ICCBS, University of Karachi, Karachi 75270, Pakistan. zssaify@gmail.com
authors.forename: Zafar Saeed
authors.initials: ZS
authors.lastname: Saify
authors.forename: Huma
authors.initials: H
authors.lastname: Rasheed
authors.forename: Nousheen
authors.initials: N
authors.lastname: Mushtaq
authors.forename: Mehrun
authors.initials: M
authors.lastname: Nisa
authors.forename: Shazia
authors.initials: S
authors.lastname: Haider
authors.forename: Afshan
authors.initials: A
authors.lastname: Naz
authors.forename: Kaniz Fizza
authors.initials: KF
authors.lastname: Azhar
authors.forename: Ghulam Abbas
authors.initials: GA
authors.lastname: Miana
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D000700:Analgesics; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D011957:Receptors, Opioid; D013928:Thromboxane A2; D001241:Aspirin