Reduction of Dizocilpine and Scopolamine-Induced Deficits in Avoidance Responding by SCH 54388, a Metabolite of Felbamate

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 1997-11, Vol.58 (3), p.657-664
• Main Authors: Smith, R.D, Grzelak, M.E, Coffin, V.L
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants - pharmacology; Avoidance Learning - drug effects; Biological and medical sciences; Dizocilpine; Dizocilpine Maleate - administration & dosage; Dizocilpine Maleate - antagonists & inhibitors; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - pharmacology; Felbamate; Injections, Subcutaneous; Male; Medical sciences; Mice; Mice, Inbred BALB C; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - pharmacology; Neuropharmacology; Passive-avoidance responding; Pharmacology. Drug treatments; Phenylcarbamates; Propylene Glycols - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Scopolamine; Scopolamine - administration & dosage; Scopolamine - antagonists & inhibitors; Scopolamine - pharmacology
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(97)00027-0

Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a novel antiepileptic agent with a unique structure and mechanism of action, possibly involving binding sites at the N-methyl-D-aspartate receptor (NMDA) complex. A monocarbamate metabolite of felbamate (SCH 54388) was compared to felbamate using a mouse passive-avoidance paradigm (PAR). SCH 54388 was markedly free of toxic side effects up to doses of 300 mg/kg, sc. SCH 54388 reduced the deficit-producing effects of either scopolamine, a cholinergic antagonist, or dizocilpine (MK-801), an NMDA receptor channel blocker, in a dose-dependent manner. The effective dose range of SCH 54388 was between 0.01 and 10 mg/kg, sc. SCH 54388 was also orally active at doses between 0.1 and 10 mg/kg. Felbamate also reduced scopolamine and dizocilpine antagonism, but was less potent than SCH 54388, reducing scopolamine-induced deficits at 1 to 3 mg/kg, sc in a dose-dependent manner and reducing deficits induced by dizocilpine at doses of 0.1 and 3 mg/kg, SC. The reduction of dizocilpine-induced deficits by felbamate was not dose dependent. These results suggest that SCH 54388 has a mechanism of action involving either directly or indirectly, glutaminergic and cholinergic central neuronal systems.