Journal article
Characterization of Pharmacological and Wake-Promoting Properties of the Dopaminergic Stimulant Sydnocarb in Rats
The Journal of pharmacology and experimental therapeutics, v 337(2), pp 380-390
01 May 2011
PMID: 21300706
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Characterization of Pharmacological and Wake-Promoting Properties of the Dopaminergic Stimulant Sydnocarb in Rats
- Creators
- John A. Gruner - CNSJoanne R. Mathiasen - CNSDorothy G. Flood - CNSMaciej Gasior - CNS
- Publication Details
- The Journal of pharmacology and experimental therapeutics, v 337(2), pp 380-390
- Publisher
- Amer Soc Pharmacology Experimental Therapeutics
- Number of pages
- 11
- Grant note
- Cephalon, Inc.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000289671600006
- Scopus ID
- 2-s2.0-79955031493
- Other Identifier
- 991021900193504721
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- Web of Science research areas
- Pharmacology & Pharmacy