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.