A review of the neuroprotective properties of the 5-HT1A receptor agonist repinotan HCl (BAYx3702) in ischemic stroke.

CNS Drug Reviews
A C BerendsC Nyakas

Abstract

Repinotan HCl (repinotan, BAYx3702), a highly selective 5-HT1A receptor agonist with a good record of safety was found to have pronounced neuroprotective effects in experimental models that mimic various aspects of brain injury. Repinotan caused strong, dose-dependent infarct reductions in permanent middle cerebral artery occlusion, transient middle cerebral artery occlusion, and traumatic brain injury paradigms. The specific 5-HT1A receptor antagonist WAY 100635 blocked these effects, indicating that the neuroprotective properties of repinotan are mediated through the 5-HT1A receptor. The proposed neuroprotective mechanisms of repinotan are thought to be the result of neuronal hyperpolarization via the activation of G protein-coupled inwardly rectifying K+ channels upon binding to both pre- and post-synaptic 5-HT1A receptors. Hyperpolarization results in inhibition of neuron firing and reduction of glutamate release. These mechanisms, leading to protection of neurons against overexcitation, could explain the neuroprotective efficacy of repinotan per se, but not necessarily the efficacy by delayed administration. The therapeutic time window of repinotan appeared to be at least 5 h in in vivo animal models, but may be even longe...Continue Reading

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