Colonic perforation in 4 dogs following treatment with meloxicam.

OBJECTIVE: To describe the clinical findings and treatment of 4 dogs that developed colonic perforation shortly after meloxicam administration. SERIES SUMMARY: Three cases were treated with meloxicam for variable nonspecific signs including lethargy and pyrexia. Hemorrhagic diarrhea developed following meloxicam administration in 2 cases. Gastrointestinal perforation was suspected on diagnostic imaging leading to exploratory celiotomy in all 3 cases. Partial colectomy was performed in 2 cases and suture repair with serosal patching in 1 followed by broad spectrum antimicrobials. All 3 dogs recovered from surgery well. One dog that had undergone perineal herniorrhaphy and received meloxicam perioperatively collapsed and died 7 days postsurgery. Postmortem examination revealed ulceration and perforation of the ascending colon with resultant generalized septic peritonitis. Histopathologic findings in all cases showed full thickness infiltration of the colonic wall with inflammatory cells along with ulceration and perforation. Thrombosis of vessels underlying the ulcerated areas was also noted. NEW OR UNIQUE INFORMATION PROVIDED: This report suggests that colonic perforation may be a complication of nonsteroidal anti-inflammatory drug use in some cases. To the authors' knowledge, this has not previously been described in dogs. Colonic perforation associated with NSAIDs administration may be more commonly identified in dogs with concurrent morbidities. Caution may be warranted when using NSAIDs in dogs with colonic pathology or possible risk factors to develop such pathology. Prompt diagnosis and treatment is essential for a positive outcome.

Discovery of a potent and selective 5-ht5A receptor antagonist by high-throughput chemistry.

High-throughput screening of an array of biphenylmethylamines synthesised by high-throughput solid-phase chemistry resulted in the identification of compounds with high-affinity for the 5-ht5A receptor. The structure-activity relationship within this series and further array synthesis led to the identification of the biphenylmethylamine derivative 11, a potent and selective 5-ht5A receptor antagonist.