SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits

• Published in: Journal of the neurological sciences 1997-12, Vol.153 (1), p.25-31
• Main Authors: Perez-Pinzon, Miguel A, Yenari, Midori A, Sun, Guo H, Kunis, David M, Steinberg, Gary K
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; Brain Ischemia - pathology; Calcium; Calcium Channel Blockers - pharmacology; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Conopeptides; Evoked Potentials, Somatosensory - physiology; Excitotoxicity; Focal cerebral ischemia; Magnetic Resonance Imaging; Male; Medical sciences; MVIIA; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - pharmacology; omega-Conotoxins; Peptides - pharmacology; Pharmacology. Drug treatments; Rabbit; Rabbits; Stroke
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(97)00196-2

Cytosolic Ca 2+ overload has been proposed as a main cause of neuronal injury during cerebral ischemia. SNX-111, a synthetic product of the naturally occurring ω-conotoxin MVIIA, is a novel, presynaptic N-type Ca 2+ channel antagonist and has been reported to be neuroprotective against cerebral ischemia. We studied the neuroprotective effects of SNX-111 in a rabbit model of focal cerebral ischemia. New Zealand white male rabbits (2.5–3.5 kg) were given 1 mg/kg/h i.v. SNX-111 ( n=8) or normal saline ( n=8) 10 min after onset of a 2-h period of transient focal cerebral ischemia induced by occlusion of the left middle cerebral, anterior cerebral and internal carotid arteries followed by 4 h reperfusion. SNX-111 significantly attenuated overall cortical ischemic neuronal damage by 44% (saline, 38.7±3.0%; SNX-111, 21.5±6.0%, P