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: Zafar Saeed Saify, Huma Rasheed, Nousheen Mushtaq, Mehrun Nisa, Shazia Haider, Afshan Naz, Kaniz Fizza Azhar, Ghulam Abbas Miana
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 35 Issue 11 Pg. 1953-9 (Nov 2012) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 23212637 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Piperidines
• Platelet Aggregation Inhibitors
• Prostaglandins
• Receptors, Opioid
• Thromboxane A2
• Aspirin

Topics

• Analgesics (administration & dosage, chemistry, pharmacology)
• Animals
• Aspirin (administration & dosage, pharmacology)
• Female
• Humans
• Inhibitory Concentration 50
• Male
• Mice
• Pain (drug therapy)
• Piperidines (administration & dosage, chemistry, pharmacology)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage, chemistry, pharmacology)
• Prostaglandins (metabolism)
• Receptors, Opioid (metabolism)
• Structure-Activity Relationship
• Thromboxane A2 (metabolism)