Effect of ifenprodil on ocular tissue circulation in rabbits

Ifenprodil tartrate has long been employed as a cerebral vasodilator with alpha and N-methyl-D-aspartate (NMDA) receptor antagonistic activities. The purpose of this study was to evaluate the effects of ifenprodil on ocular circulation in rabbits. Experiments were performed during the dark phase in Dutch rabbits conditioned to a schedule of alternating 12-hr periods of light and dark. Effects on ocular tissue blood velocity were estimated using the laser speckle method in the iris, posterior choroid, and optic nerve head (ONH). Measurements of tissue blood velocity were performed both after intravenous injection of ifenprodil at a dose of 0.2 mg/kg, 0.1 mg/kg, and the same volume of the vehicle, and after topical instillation of 0.5% ifenprodil (50 microl) twice daily for 1, 3 and 20 days unilaterally in a masked manner. Intraocular pressure (IOP) was also measured during the experimental period. Intravenous administration of ifenprodil caused a significant increase in blood velocity in the ONH, choroid, and iris, but ONH circulation was affected at a lower dose than uveal circulation. In the topical instillation experiment, IOP in the ifenprodil-treated eye was significantly lower, by approximately 2 mmHg, than that in the contralateral eye when the laser speckle measurement was performed. Twice-daily, unilateral 0.5% ifenprodil instillation significantly increased blood velocity in the iris after 3 days and that in the ONH and posterior choroid after 20 days in the treated eye. Topical 0.5% ifenprodil increased blood velocity in the iris, posterior choroid, and ONH after multiple dosings. After systemic administration, ONH circulation appeared to be influenced at a lower dose than was uveal circulation.