Further evaluation of a series of anti-inflammatory N-pyrrolylcarboxylic acids: effects on the nociception in rats.
The analgesic activity of nine substituted N-pyrrolylcarboxylic acids, previously reported as anti-inflammatory agents, has been evaluated. The effects on nociception were examined in male Wistar rats by the Randall-Selitto paw-pressure test. The compounds were administrated in doses 10, 20, and 40 mg/kg both i.p. and p.o. As a whole, the activities of 3-(N-pyrrolyl)propanoic acids 3e-3h and 2-[3-(ethoxycarbonyl)-2-methyl-5-phenyl-1H-1-pyrrolyl]-3-methylpentanoic acid 3i were comparable with or superior to that of metamizole used as a reference (200 mg/kg, i.p.), whereas only 3a from among the N-pyrrolyl-acetic acids 3a-3d showed analgesic activity on the inflamed paw. The compounds found most promising to increase the pain threshold significantly were the same ones with the higher anti-inflammatory activity registered in our previous study: 3-[3-(ethoxycarbonyl)-2-methyl-5-(3-nitrophenyl)-1H-1-pyrrolyl]propanoic acid 3e, together with its 5-(4-nitrophenyl)- 3f, 5-phenyl- 3g, and 5-(4-methylphenyl)- 3h analogs. Certain parallels between the analgesic activities and some physicochemical properties were observed.
Bocheva
Adriana
A
Department of Pathophysiology, Medical University, Sofia, Bulgaria.
Bijev
Atanas
A
Nankov
Atanas
A
D000698:Analgesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D008297:Male; D010147:Pain Measurement; D011758:Pyrroles / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011758:Pyrroles