Iptakalim hydrochloride (IPT) is a novel ATP-sensitive potassium (KATP) channel opener which has a different chemical structure from any other known KATP channel opener, and exhibits both blood-brain barrier permeability and little side effects after systemic administration. Emerging lines of evidence indicate that IPT effectively protects brain neurons against glutamate neurotoxicity in in vitro and in vivo animal ischemic/hypoxic models. In addition, IPT has also been shown to serve as a potent compound that protects substantia nigra dopamine neurons against a variety of chemical stresses (e.g., MPP+, 6-OHDA or rotenone) in in vitro and in vivo Parkinsons disease animal models. Possible pharmacological mechanisms of neuroprotection induced by IPT involve the opening of cytoplasmic and mitochondrial KATP channels, diminishing glutamatergic synaptic transmission by blocking presynaptic glutamate release, reducing postsynaptic ionotropic glutamate receptor-especially NMDA receptor-function, enhancing extracellular glutamate uptake, and reducing Ca2+ release from intracellular Ca2+ stores. Since it acts on multiple central targets in order to exert neuroprotective effects, IPT is a high-potential, promising candidate for the prevention and treatment of neurodegeneration-relevant disorders. Therefore, IPT is not only a useful pharmacological tool for KATP channel investigation, but it also serves as a novel, high-potent, low-toxic, therapeutic agent that protects brain neurons against a variety of neurodegenerative diseases.