In recent decades, consumption of psychostimulants has been significantly increased all over the world, while exact mechanisms of neurochemical effects of psychomotor stimulants remained unclear. It is assumed that the neuronal messenger nitric oxide (NO) may be involved in mechanisms of neurotoxicity evoked by psychomotor stimulants. However, possible participation of NO in various pathological states is supported mainly by indirect evidence because of its short half-life in tissues. Aim of this review is to describe the involvement of NO and the contribution of lipid peroxidation (LPO) and acetylcholine (ACH) release in neurotoxic effects of psychostimulant drugs. NO was directly determined in brain structures by electron paramagnetic resonance (EPR). Both NO generation and LPO products as well as release of ACH were increased in brain structures following four injections of amphetamine (AMPH). Pretreatment of rats with the non-selective inhibitor of NO-synthase (NOS) N-nitro-L-arginine or the neuronal NOS inhibitor 7-nitroindazole significantly reduced increase of NO generation as well as the rise of ACH release induced by AMPH. Both NOS inhibitors injected prior to AMPH had no effect on enhanced levels of LPO products. Administration of the noncompetitive NMDA receptor antagonist dizocilpine abolished increase of both NO content and concentration of LPO products induced by of the psychostimulant drug. Dizocilpine also eliminated the influence of AMPH on the ACH release. Moreover, the neurochemical and neurotoxic effects of the psychostimulant drug sydnocarb were compared with those of AMPH. Single injection of AMPH showed a more pronounced increase in NO and TBARS levels than after an equimolar concentration of sydnocarb. The findings demonstrate the crucial role of NO in the development of neurotoxicity elicited by psychostimulants and underline the key role of NOS in AMPH-induced neurotoxicity.

01 May 2011·Journal of Pharmacology and Experimental TherapeuticsQ3 · MEDICINE

Characterization of Pharmacological and Wake-Promoting Properties of the Dopaminergic Stimulant Sydnocarb in Rats

Q3 · MEDICINE

Article

Author: Gasior, Maciej ; Flood, Dorothy G. ; Mathiasen, Joanne R. ; Gruner, John A.

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 (EC(50) = 0.10 μM; 95% confidence limits, 0.06-0.18), sydnocarb (up to 100 μM) 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 μM). Sydnocarb at 10 μM 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.

01 Aug 2010·PsychopharmacologyQ3 · MEDICINE

The effects of d-amphetamine, methylphenidate, sydnocarb, and caffeine on prepulse inhibition of the startle reflex in DBA/2 mice

Q3 · MEDICINE

Article

Author: Eva Zuvich ; Maciej Gasior ; Dorothy G. Flood ; Michael J. Marino

RATIONALEDopamine (DA) agonists decrease prepulse inhibition (PPI) and are widely used in translational models for the sensorimotor gating deficits in schizophrenia. Reductions in PPI induced by DA agonists are routinely reversed by antipsychotics in these translational models. Nevertheless, under conditions of low-baseline PPI, DA agonists may increase PPI in humans and experimental animals. DBA/2 mice have naturally low-baseline PPI, which as in the drug-induced translational models, is increased by antipsychotics.OBJECTIVEDetermine whether DBA/2 mice respond like other models of low-baseline PPI by evaluating the effect of psychostimulants (caffeine, 30-100 mg/kg IP) and the indirect DA agonists d-amphetamine (0.3-10 mg/kg IP), methylphenidate (10-100 mg/kg IP), and sydnocarb (10-30 mg/kg IP), a selective DA transporter inhibitor on PPI. Furthermore, baseline PPI in DBA/2 mice was increased by noise exposure and the effect of d-amphetamine was assessed.RESULTSPPI was increased at one dose for each of the psychostimulants when baseline PPI was low in naïve DBA/2 mice. Effective doses were 3 mg/kg of d-amphetamine, 30 mg/kg of methylphenidate, 30 mg/kg of sydnocarb, and 100 mg/kg of caffeine. Higher doses of d-amphetamine (10 mg/kg) and methylphenidate (100 mg/kg IP) decreased PPI. When the baseline PPI was increased by noise exposure, 10 mg/kg of d-amphetamine only reduced PPI.CONCLUSIONLower doses of psychostimulants increased PPI in naïve DBA/2 mice in a manner consistent with their naturally low-baseline PPI, and higher doses decreased PPI, consistent with effects observed in most mouse strains.

100 Deals associated with Sydnocarb

External Link

KEGG	Wiki	ATC	Drug Bank
-	Sydnocarb	N05A	-

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Behavioural disorders	RU	Teva Pharmaceutical Industries Ltd.	01 Jan 1970

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis