HYPERTROPHIC OSTEOPATHY IN RATS FOLLOWING CHRONIC ADMINISTRATION OF SDZ-MNS-949, AN ISOQUINOLINE

SDZ MNS 949, 6,7-dimethoxy-3-methyl-1-(3',5'-bis (methoxyethoxy) pheny l)-isoquinoline, a bronchodilating antiinflammatory drug that inhibits phosphodiesterase, had been proposed for the treatment of bronchial a sthma. Groups of 14 male and 14 female Wistar rats were administered d oses of 12, 50, and 130 mg/kg/day in feed for 26 weeks. Periodic radio graphic examinations were performed in addition to clinical observatio ns, clinical chemistry measurements and urinalysis. At study terminati on full necropsy and histopathological examinations were performed on all animals. The principal clinical signs observed were unilateral ede matous, red and painful swelling of the distal hindlimbs in 8 of 28 hi gh dose animals, and abdominal swelling in 19 of 28 high dose animals. At radiographic examination periosteal new bone formation was predomi nantly along the tibia. Lesions at necropsy included dilated small and large intestines. Microscopically, enteritis was observed, and the pe riosteal new bone formation was confirmed. Hematological findings cons isted of thrombocytosis and lymphocytosis, especially in high dose ani mals. The clinical, radiographical and histological findings in treate d rats were consistent with the diagnosis of ''hypertrophic osteopathy '' or ''Marie's Disease''.