Gavestinel

Gavestinel (GV-150,526) was an investigational drug developed by GlaxoSmithKline for acute intracerebral hemorrhage, which in 2001 failed to show an effect in what was at the time, the largest clinical trial in stroke that had been conducted.

Gavestinel is an NMDA antagonist, binding selectively to the glycine site on the NMDA receptor complex, rather than the glutamate site many NMDA antagonists bind to.

Pharmacology and Toxicology

N-methyl-D-aspartate (NMDA) receptors are amino acid receptors, overstimulation to which lead to increased intracellular Ca²⁺ level, and become deleterious to neural cell. In ischaemic or hypoxic conditions such as stroke, the concentration of glutamate in synaptic clefts is increased, and continuously stimulates NMDA recpetors. Gavestinel was synthesized by substituting indole-2-carboxylate at the C-3 position with an unsaturated lateral side chain. It binds to NMDA receptor on the glycine site with high affinity, selectivity and a broad time window efficacy, thus gains interests in testing its efficacy in treating stroke. In pre-clinical studies, gavestinel showed no significant side effects on memory, learning, and cardiovascular system, side effects that are very common in NMDA antagonists.