Disease relevance of Aptiganel

• Both noncompetitive (aptiganel hydrochloride, dextrorphan) and competitive (selfotel, d-CPPene) antagonists have undergone tolerability studies in acute stroke and traumatic brain injury [1].
• CERESTAT (4, aptiganel CNS 1102) is currently undergoing clinical trial for the treatment of traumatic brain injury and stroke [2].
• Aptiganel HCl reduced contusion volume by 13.6% in treated rats (p < 0.05) [3].
• Aptiganel HCl causes elevation of blood pressure and is associated with central nervous system symptoms and signs similar to other noncompetitive NMDA antagonists [4].
• Recent studies revealed a neuroprotective effect of the non-competitive NMDA receptor antagonist Aptiganel HCL (Cerestat CNS 1102) in focal cerebral ischemia [5].

High impact information on Aptiganel

• In human volunteers, dose-limiting effects of aptiganel are blood pressure increases and central nervous system (CNS) excitation or depression [6].
• Clinical experience suggests that although some NMDA antagonists are poorly tolerated at putative neuroprotective doses (e.g., selfotel), potentially neuroprotective plasma concentrations can be achieved in humans with others (e.g., aptiganel), though tolerable adverse effects are frequently observed [7].
• Although recent studies with selfotel and eliprodil have been discontinued because of insufficient evidence for a satisfactory risk/benefit ratio, encouraging experience with aptiganel, magnesium, and glycine antagonists has prompted continued clinical trials with these agents [7].
• Aptiganel inhibits c-Jun expression, attenuates neuronal necrosis, and improves outcome [8].
• Immediate-early gene expression in ovine brain after hypothermic circulatory arrest: effects of aptiganel [9].

Chemical compound and disease context of Aptiganel

• Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists (competitive receptor antagonists, ion channel blockers, and glycine antagonists)--such as selfotel, aptiganel, eliprodil, licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury [10].

Associations of Aptiganel with other chemical compounds

• Development of the NMDA ion-channel blocker, aptiganel hydrochloride, as a neuroprotective agent for acute CNS injury [11].

Analytical, diagnostic and therapeutic context of Aptiganel

• CONCLUSIONS: A 4.5-mg intravenous bolus of aptiganel HCl followed by infusion of 0.75 mg/h for 12 hours is a tolerable dose that can produce plasma drug concentrations shown to be neuroprotective in animal models [6].
• The non-competitive antagonist, aptiganel, is currently in Phase III clinical trials and its therapeutic efficacy and index should be defined in 1997 and 1998 [12].

References