CHRONIC TOLERANCE STUDIES ON -DIETHYLAMINOETHYL XANTHENE-9-CARBOXYLATE METHOBROMIDE (BANTHINE)

¹ Division of Biological Research, G. D. Searle and Co. , Chicago 80

The effects of prolonged oral administration of Banthine were studied in the rat and dog.

Rats. The chronic tolerance study was made on two separate series of rats. It was carried through two generations of animals in one series at approximate daily doses of 415 and 208 mgm./kgm., and through three generations in the other series at approximately 208 and 104 mgm./kgm./day, for periods ranging between 100 and 343 days. These three doses represented m=1/4, m=1/8 and 1/16, respectively, of the rat acute intragastric LD₅₀. These treatments had no apparent effect on general appearance, behavior or reproduction of the animals. Out of a total of 163 rats receiving Banthine only ten died: one at 415 mgm., nine at 208 mgm., and none at 104 mgm./kgm. No other signs of toxicity were evidenced except for retardation of growth, which was small but significant only in some of the second and third generation male groups.

Dogs. Three dosage levels were used for the dog chronic tolerance study, 115 mgm. (6 dogs), 58 mgm. (7 dogs), and 29 mgm./kgm. (4 dogs). These doses were given in capsule form five days weekly. Side effects of mydriasis and xerostomia were common at all three levels. There was no evidence of toxicity by periodic clinical laboratory tests. Three animals, two receiving the highest and one the middle dose, died during the study following signs resembling acute curare intoxication. Another at the highest dose died of a severe generalized infection. The remaining thirteen dogs were sacrificed at various intervals. No gross or microscopic lesions due to Banthine were found, regardless of dosage.