Stroke — repinotan
Stroke is one of the major causes of death and disability in the developed world. A stroke occurs when the blood supply to the brain is interrupted. An ischaemic stroke results from a thrombosis or embolism, and a haemorrhagic stroke from the rupture of an artery wall. It causes weakness, usually in one side of the body, and can vary in severity from a mild tingling to paralysis and death. An effective drug treatment that reduced the severity of the symptoms would be of great benefit.
Some drugs have uses in the treatment of strokes, particularly the ischaemic type, including clot-busting drugs as primary therapy and low doses of blood-thinning agents, notably aspirin, as a preventative measure.
More recently, there has been work on neuroprotective drugs to be given as soon as possible after the stroke has occurred that are intended to reduce, or even repair, the damage caused by the lack of blood flow in the brain.
One such drug being investigated by Bayer is the 5-HT1A agonist repinotan hydrochloride, formerly known as Bay-x-3702. In vivo studies on its efficacy in improving cognitive performance and attenuating neuronal loss in rats showed a decrease in both neuronal loss and cortical tissue loss.1 Both in vitro and in vivo studies demonstrate that its neuroprotective activity may result from the inhibition of glutamate release, with rat studies showing that cortical extra-cellular glutamate was about 50% lower in treated rats than the control group, and there was no alteration in aspartate levels.2
A further rat model study indicated that stimulating the 5-HT1A receptors rescued striatal and hippocampal neurons from apoptotic cell death. Raising the level of repinotan given past a certain point led to no improvement, which was attributed to a reduction in arterial blood pressure.3 Acute human stroke patients have been given the agent in a Phase II dose finding study, and it was found to be well tolerated, and improved both the neurological and functional outcomes at doses of 1.25mg/day over three days.4