Stroke - EAA-090
Stroke is one of the most common causes of death in the developed world. Ischaemic stroke results from a thrombosis or embolism, leading to weakness, often focused in one side of the body, and its symptoms can be as limited as mild tingling or as extreme as paralysis. Various classes of drugs are used in the treatment of clots, with clot-busting drugs being used as primary therapies, and blood thinning agents being used prophylactically.
Following problems with a range of neuroprotective drugs in the trials stages, there is still a need for effective, safe treatments for acute ischaemic stroke. One mechanism of action that is receiving much attention at the moment is blocking the N-methyl-D-aspartate (NMDA) receptors that are involved in the cascade leading to the elevated calcium levels that ultimately trigger off a process which ends in neuronal cell death.
A new selective NMDA antagonist that is undergoing clinical trials is EAA-090.1 Being developed by Wyeth, it was shown in in vitro studies to be a potent, selective competitive NMDA antagonist.
A study to evaluate its safety and tolerability was carried out in 40 healthy male volunteers. The subjects were randomised to receive either placebo or EAA-090 as an intravenous bolus over 15 minutes, with escalating doses of 30–960mg. No significant changes in the mean arterial blood pressure were seen with doses of up to 480mg. Rises in blood pressure peaked at 30min for patients given all doses other than the highest, and the pressure returned to normal after two hours. No serious adverse effects were seen.
Doses of up to 120mg gave no CNS effects, and only minimal ones up to 600mg. Dizziness was the most common side-effect; others included poor concentration and tingling sensations. As a result, it was established that single doses of up to 720mg were well tolerated, and clinical trials continue. It appears not to have the problems that dogged earlier NMDA antagonists, and could prove to be a breakthrough in the treatment of stroke.