BACKGROUNDalpha(1)-Acid glycoprotein (AGP) plays a decisive role in the serum protein binding of several drugs.Genetic variants of AGP have different ligand binding properties. The binding of deramciclane (DER), a chiral anxiolytic agent, has been studied on A and F1/S genetic variants of AGP.METHODSThe effects of DER and reference drugs on the binding of specific fluorescent and circular dichroism (CD) probes of AGP were determined. Dicumarol (DIC) binding was measured by CD and equilibrium dialysis.RESULTSDER effectively displaced probes bound to variant A, while it was less effective at displacing probes bound to variant F1/S. DER increased the binding and inverted the induced CD spectrum of DIC in the solution of variant F1/S. This phenomenon could not be brought about by the enantiomer of DER.CONCLUSIONDER has high-affinity binding (K(a)> or =2x10(6) M(-1)) to variant A, while its binding to the variant F1/S is about thirty times weaker. During simultaneous binding of DER and DIC to variant F1/S a ternary complex having about four times higher affinity is formed, in which the opposite chiral conformation of DIC is favored.GENERAL SIGNIFICANCEThe binding interactions found prove that AGP can simultaneously accommodate different ligand molecules. Even weakly bound ligands can provoke unexpected allosteric protein binding interactions.

01 Feb 2010·Pharmacology Biochemistry and BehaviorQ4 · PSYCHOLOGY

Deramciclane improves object recognition in rats: Potential role of NMDA receptors

Q4 · PSYCHOLOGY

Article

Author: György Lévay ; István Gacsályi ; Gábor Kapus ; Szabolcs Kertész

The cognition-enhancing properties of deramciclane (N,N-dimethyl-2-([(1R,4R,6S)-1,7,7-trimethyl-6-phenyl-6-bicyclo[2.2.1]heptanyl]oxy)ethanamine) and memantine (3,5-dimethyl-tricyclo[3.3.1.1(3,7)]decylamine-3,5-dimethyladamantan-1-amine) were evaluated in the novel object recognition (OR) test in the rat, while their effect in comparison with other N-methyl-D-aspartate (NMDA) receptor blockers such us MK-801 ([+]-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate) and CPP ([+/-]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) on NMDA-evoked spreading depression (SD) was investigated in the chicken retina, in vitro. In the OR test, pretreatment of rats with either deramciclane (30 mg/kg p.o.) or memantine (10 and 30 mg/kg, p.o.) resulted in preference for the novel object, compared to the familiar one, indicating procognitive activity of the compounds. In the in vitro studies memantine (10-30 M), or deramciclane (30-100 M) as well as CPP (0.1-1 M), MK-801 (0.3-1 M), concentration-dependently inhibited NMDA evoked SD. Furthermore, the inhibitory effect of memantine, deramciclane and MK-801 was activity-dependent. These results support the role of NMDA receptors in the procognitive effect of deramciclane.

01 Jan 2008·Basic & Clinical Pharmacology & ToxicologyQ3 · MEDICINE

Comparison of the Effects of Deramciclane, Ritanserin and Buspirone on Extracellular Dopamine and Its Metabolites in Striatum and Nucleus Accumbens of Freely Moving Rats

Q3 · MEDICINE

Article

Author: Tiina M. Kääriäinen ; Mikko Käenmäki ; Marko Lehtonen ; Pekka T. Männistö ; Jouko Savolainen ; Markus M. Forsberg

Abstract: In the present study, we assessed the effect of single graded doses of a putative anxiolytic compound, the 5‐HT2A/C antagonist, deramciclane fumarate (EGIS‐3886), on the dopamine efflux and metabolism in nucleus accumbens and striatum and thus evaluated the dose window for deramciclane to cause adverse effects related to the brain dopaminergic system. Dual probe in vivo microdialysis in freely moving rats was used to compare the effects of graded doses of deramciclane fumarate (3, 10 and 30 mg/kg), 5‐HT2A/C antagonist ritanserin (1 mg/kg) and a partial 5‐HT1A agonist buspirone hydrochloride (5 mg/kg) on the extracellular levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in nucleus accumbens and striatum assayed by high performance liquid chromatography with electrochemical detection. The indirect dopamine agonist, D‐amphetamine sulfate (2 mg/kg), was used as a positive control. Ritanserin, buspirone and deramciclane 3 and 10 mg/kg had no significant effects on the extracellular dopamine levels in either brain area but deramciclane 30 mg/kg significantly increased accumbal dopamine as well as DOPAC and HVA in both brain areas. As expected, the positive control D‐amphetamine significantly increased both striatal and accumbal dopamine levels. The effects of buspirone or the highest deramciclane dose and D‐amphetamine on DOPAC and HVA levels were opposite; buspirone and deramciclane increased while D‐amphetamine decreased the metabolite levels in both brain areas. The results indicate that a single high dose of deramciclane has the neuroleptic‐ or buspirone‐like effect, particularly in mesolimbic regions. There is at least a 5‐fold margin between the anxiolytic and neuroleptic doses of deramciclane in the rat.

100 Deals associated with Deramciclane fumarate

External Link

KEGG	Wiki	ATC	Drug Bank
-	Deramciclane fumarate	-	DB06512

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Anxiety Disorders	Phase 2	US	-	-
Anxiety Disorders	Phase 2	-	Pfizer Inc.	-
Anxiety Disorders	Phase 2	-	Orion Oyj	-
Anxiety Disorders	Phase 2	-	Egis Gyógyszergyár Zrt.	-
Anxiety Disorders	Phase 2	ZA	-	-
Anxiety Disorders	Phase 2	FI	Orion Oyj	-
Anxiety Disorders	Phase 2	-	-	-
Seizures	Discovery	HU	Hungarian Academy of Sciences	01 Mar 1989

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