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KMID : 0043320120350111953
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Archives of Pharmacal Research
2012 Volume.35 No. 11 p.1953 ~ p.1959
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Investigation of piperidine derivatives in ex vivo models of pain and platelet aggregation
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Saify Zafar Saeed
Rasheed Huma
Mushtaq Nousheen
Nisa Mehrun
Haider Shazia
Naz Afshan
Azhar Kaniz Fizza
Miana Ghulam Abbas
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Abstract
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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 A. 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 IC50 = 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 IC50 = 80 mM. Acetyl salicylic acid (IC50 = 150 μM) was used as a positive control.
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KEYWORD
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Pain, Opoid receptor, Platelet aggregation, Platelet activating factor
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