SGB‐017 (ADCI): A Novel Anticonvulsant with a Dual Mechanism of Action

SGB-017, also known as (+)ADCI, NGB-812 or WAY-143017, is a novel anticonvulsant with two known mechanisms of action. It inhibits N-methyl-d-aspartate (NMDA) receptor channels in a noncompetitive and use-dependent manner (13,24), and like many standard anticonvulsants (i.e., carbamazepine, phenytoin, and lamotrigine), SGB-017 also blocks sodium channels in a voltage-dependent manner (28,31). The dual action of blocking both NMDA as well as sodium channels, suggests that SGB-017 may be useful in treating some epilepsies that are resistant to carbamazepine or phenytoin treatment. In the anticonvulsant-screening program at the Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Health (NIH), SGB-017 was found to be a moderately potent anticonvulsant with a good margin of safety. Like carbamazepine, SGB-017 was effective in preventing seizures induced by maximal electroshock (MES) and by potassium channel blockers, such as dendrotoxin or 4-aminopyridine, but was ineffective against pentylenetetrazol-, bicuculline-, or strychnine-induced seizures (5,24,34). Unlike carbamazepine, it also prevented seizures induced by ethanol withdrawal, cocaine, or NMDA, and retarded the onset of kindled seizures (12,24,27). The latter types of seizures are typically unresponsive to sodium channel blockers, but can be inhibited by NMDA antagonists, such as dizocilpine (MK-801). Although it acts at the same site as MK-801 and phencyclidine (PCP), SGB-017 does not have any of the liabilities associated with NMDA antagonists in animal models, such as psychotomimetic effects, deficits in cognition, or neurotoxicity (14,20). It does not substitute for MK-801 in rats trained to discriminate between MK-801 and saline (11). In various rat behavioral models, SGB-017 produced neither deficits in learning and memory nor vacuolizations or lesions in the brain, which are typically associated with NMDA an-