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[摘要]：Sydnocarb is a psychomotor stimulant structurally similar to D-amphetamine (D-AMPH) and is used in Russia for the treatment of a variety of neuropsychiatric comorbidities. The nature of sydnocarb-induced facilitation of dopamine (DA) neurotransmission [DA release versus DA transporter (DAT) inhibition] is not clear. The present study characterized the pharmacological actions and behavioral effects of intraperitoneal sydnocarb in male Sprague-Dawley rats. Where relevant, comparisons were made with intraperitoneal D-AMPH. Unlike D-AMPH, which causes release of DA from rat synaptosomes (EC50 = 0.10 mu M; 95% confidence limits, 0.06-0.18), sydnocarb (up to 100 mu M) did not. Sydnocarb potently (K-i = 8.3 +/- 0.7 nM) blocked recombinant human DAT expressed in Chinese hamster ovary-K1 cells and less potently blocked the norepinephrine transporter (K-i = 10.1 +/- 1.5 mu M). Sydnocarb at 10 mu M did not bind to 64 other targets. In rats, 10 and 30 mg/kg sydnocarb showed a 2-fold longer half-life in plasma and brain and a 5-fold lower brain-to-plasma ratio compared with 0.3 and 1 mg/kg D-AMPH. In the Irwin assay, sydnocarb was well tolerated up to 30 mg/kg; D-AMPH-like stereotypic behaviors were evident at 100 mg/kg. Behavioral effects of 30 mg/kg sydnocarb and 0.3 mg/kg D-AMPH were comparable. In a sleep/wake assay, 10 mg/kg sydnocarb and 1 mg/kg D-AMPH increased wakefulness comparably; however, sydnocarb (up to 30 mg/kg) did not induce D-AMPH-like rebound hypersomnolence (RHS). Like D-AMPH, sydnocarb enhanced theta power, an electrophysiological measure of cognitive function. In conclusion, sydnocarb is a selective and potent DAT inhibitor that produces robust increases in the wake state without RHS, and with potential cognitive-enhancing properties. |
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