Ocular Toxicity in Beagle Dogs with Lortalamine, A Non Tricyclic Antidepressant Compound

ABSTRACT

During a preclinical safety evaluation study, an indication of ocular toxicity was noted in beagle dogs receiving orally (gelatin capsules) once a day, 7 days a week for, respectively, 7 and 91 days, 10 mg/kg/day of Lortalamine, a new non-tricyclic anti-depressant compound. Lortalamine treated dogs showed, progressively, bilateral mydriasis, conjunctivitis, epiphora, corneal oedema and corneal erosions from day 2 to day 7. Thereafter, even though treatment goes on, ocular lesions were progressively improved, and inflammation and swelling of both cornea slowly reversed, especially from day 8 to 30. These ocular changes were very similar to those reported with sympathomimetic agents. It was speculated that these lesions, following chronic oral administration of Lortalamine which induced high levels of the compound and its metabolite in the cornea, were related to an increased binding of norepinephrine to adrenergic receptors since the compound inhibits the re-uptake of the transmitter into the storing vesicles.