3417 Retinal vascular disruption associated with gestational exposure to cocaine

Puroose: The present study investigated whether flupirtine, a nonopioid analgesic agent with some NMDA antagonistic properties in viva and in vitro, protects from ischaemic retinal injury. Methods and Results: Retinal ischaemia was induced either by transient occlusion of both common carotid arteries in the rat or by a “suction cup procedure” which raises the intraocular pressure in the rabbit. lschaemia caused a reduction in the b-wave of the electroretinogram of rats and rabbits and a change in the nature of the normal GABA immunoreactivity of rabbit retina. Flupirtine given either intraperitoneally or into the vitreous humour significantly enhanced the recovery of the reduced b-wave of the electroretinogram after reperfusion and reduced the changes in the GABA-immunoreactivity. Exposure to rabbit retinas to kainate or NMDA in vitro each caused a characteristic change in the GABA immunoreactivity. Flupirtine counteracted the influence produtBd by NMDA but had no effect on the kainate responses. Rat retinas incubated in vitro in physiological solution containing flupirtine caused a significant rise in the tissues ATP content compared with control samples. When the oxygen in the physiological solution was displaced with nitrogen the retinal ATP levels dropped significantly. Addition of flupirtine prevented this decrease from taking place because of a lack of oxygen. Conclusions: The combined data show that flupirtine is a neuroprotective agent in retinal ischaemia and that the mode of its mechanism of action involves antagonism of NMDA responses and increase of tissue ATP levels.