Deramciclane (EGIS-3886)
(Synonyms: 德伦环烷,EGIS-3886) 目录号 : GC33722
Deramciclane (EGIS-3886) 对 5-HT2A 和 5-HT2C 受体具有高亲和力；它作为两种受体亚型的拮抗剂，在没有直接刺激激动剂的情况下对 5-HT2C 受体具有反向激动剂特性。
Cas No.:120444-71-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[2] Male Wistar rats are used. Samples for determination of basal levels of dopamine, DOPAC and HVA are collected for 60 min. and after that the drugs (doses refer to the salts) are given intraperitoneally in a volume of 5 mL/kg of body weight. Treatments are Deramciclane fumarate 3 mg/kg (=7.2 µmol/kg), 10 mg/kg (=24 µmol/kg) and 30 mg/kg (=72 µmol/kg); D-amphetamine sulfate 2 mg/kg (=5.4 µmol/kg); Ritanserin 1 mg/kg (=2.1 µmol/kg) and Buspirone hydrochloride 5 mg/kg (=12 µmol/kg). All drugs are suspended in 0.5% carboxymethylcellulose (CMC) dissolved in 0.9% saline. Vehicle control group (n=5) are injected intraperitoneally with 5 mL/kg of 0.5% CMC solution. There are nine rats in each treatment group.The doses of Deramciclane fumarate are considered to produce plasma levels comparable to therapeutic plasma levels in human beings (3 mg/kg) or about three times higher (10 mg/kg) 1-3 hr after the administration of the drug. Behavioural data from earlier Deramciclane studies in rats indicates that Deramciclane has some antidopaminergic activity at high doses (20-40 mg/kg). The highest dose of Deramciclane (30 mg/kg) is selected in this dose range. Fairly high doses of the reference drugs are chosen based on the literature and our own experience to detect the ability of selected drugs to modify extracellular dopamine levels in either the striatum or the nucleus accumbens. After administration of each drug, samples are collected for 240 min. and then divided into two aliquots (35 µL/15 µL). The first aliquot of the samples is stored at 4°C and assayed for dopamine within 24 hr. The other aliquot is frozen and stored at -70°C until assayed for DOPAC and HVA. |
References: [1]. P lvim ki EP, et al. Deramciclane, a putative anxiolytic drug, is a serotonin 5-HT2C receptor inverse agonist but fails to induce 5-HT2C receptor down-regulation. Psychopharmacology (Berl). 1998 Mar;136(2):99-104. | |
Deramciclane has a high affinity for 5-HT2A and 5-HT2C receptors; it acts as an antagonist at both receptor subtypes and has inverse agonist properties at the 5-HT2C receptors without direct stimulatory agonist.
Deramciclane is a novel anxiolytic agent that binds with high affinity to 5-HT2A/2C receptors. The interactions of Deramciclane with the serotonin 5-HT2C receptor are characterized further using receptor phosphoinositide hydrolysis assays and receptor autoradiography. Deramciclane antagonizes 5-HT2C receptor mediated 5-HT-stimulated phosphoinositide hydrolysis with an IC50 value of 168 nM. Deramciclane also decreases basal phosphoinositide hydrolysis by up to 33% (EC50= 93 nM) in a physiological system in the choroid plexus, suggesting that Deramciclane possesses inverse agonist properties at this receptor[1].
Deramciclane 3 and 10 mg/kg does not change the dopamine levels significantly at any time point versus the basal level whereas 30 mg/kg of Deramciclane significantly increases the levels at 40-100 min and at 160-240 min (P<0.05). Deramciclane is a putative antiserotonergic compound that reduces 5-HT-induced phosphoinositol hydrolysis and a variety of actions caused by serotonergic agonists. The receptor binding profile of Deramciclane is rather similar to that of ritanserin. Deramciclane has a high affinity for 5-HT2A and 5-HT2C receptors; it acts as an antagonist at both receptor subtypes and has inverse agonist properties at the 5-HT2C receptors without direct stimulatory agonist effects. Deramciclane has been shown to have anxiolytic-like activity in several animal tests[2].
[1]. P?lvim?ki EP, et al. Deramciclane, a putative anxiolytic drug, is a serotonin 5-HT2C receptor inverse agonist but fails to induce 5-HT2C receptor down-regulation. Psychopharmacology (Berl). 1998 Mar;136(2):99-104. [2]. K??ri?inen TM, et al. Comparison of the effects of deramciclane, ritanserin and buspirone on extracellular dopamine and its metabolites in striatum and nucleus accumbens of freely moving rats. Basic Clin Pharmacol Toxicol. 2008 Jan;102(1):50-8.
| Cas No. | 120444-71-5 | SDF | |
| 别名 | 德伦环烷,EGIS-3886 | ||
| Canonical SMILES | CC1(C)[C@]2(C)[C@@](OCCN(C)C)(C3=CC=CC=C3)C[C@@]1([H])CC2 | ||
| 分子式 | C20H31NO | 分子量 | 301.47 |
| 溶解度 | DMSO : 100 mg/mL (331.71 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3171 mL | 16.5854 mL | 33.1708 mL |
| 5 mM | 0.6634 mL | 3.3171 mL | 6.6342 mL |
| 10 mM | 0.3317 mL | 1.6585 mL | 3.3171 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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Deramciclane (Egis)
Curr Opin Investig Drugs 2002 Feb;3(2):289-94.PMID:12020062doi
Egis, in collaboration with Orion Pharma and Pharmacia, is developing Deramciclane, a 5-HT(2A) antagonist and a 5-HT(2C) inverse agonist, as a potential treatment for anxiety disorders [300642]. The compound was also in development for epilepsy but no recent development has been reported for this indication. As of May 2001, comprehensive phase III studies with Deramciclane in ten European countries were progressing according to plan [399853], [408534]. By August 2001, phase III studies were also underway in South Africa [420313]. In November 2001, Pharmacia indicated that NDA filing is expected to take place in 2004 [431903]. In February 2001, Orion announced its intention to commercialize Deramciclane globally [399853]. In August 2001, Orion and Pharmacia signed an agreement under which the two companies were to collaborate in the development and commercialization of Deramciclane in the US [420313]. Analysts at Morgan Stanley predicted in November 2001, that Deramciclane would make sales of $25 million in 2004, rising to $150 million in 2005 [435320]. Analysts at Lehman Brothers predicted in December 2001, that Deramciclane had a 75% chance of being marketed by 2004, with peak sales potential of $450 million [434768].
Distribution of Deramciclane (EGIS-3886) in rat brain regions
Eur J Drug Metab Pharmacokinet 1998 Apr-Jun;23(2):125-31.PMID:9725469DOI:10.1007/BF03189327.
The time related distribution and pharmacokinetics of double-labelled EGIS-3886 (EGIS-3886-phenyl-14C and -ethyl-3H) were studied in the plasma, hypophysis and 14 cerebral regions, including the spinal cord of the rat after a single oral treatment (acute experiments) and after repeated administration of one dose daily for six days (subacute experiments). The tissue levels of EGIS-3886 (deramciclane) were calculated from the simultaneously determined dpm values and the specific activities of the two radioisomers present in the dose administered. EGIS-3886 was rapidly absorbed from the gastrointestinal tract (t(max)=1.0 h). The concentration-time curves in the tissues can be described by a two compartment open model. The 3H-activity could be measured during the whole period of the acute experiment (96 h), whereas 14C-radioactivity fell below the detection limit within 24 h. The AUC(0-96) values for 3H were 10 to 15 times higher than that for 14C. In all samples examined, on the concentration time curves a peak characteristic of enterohepatic cycle can be seen at 12 h. The studies indicated that intact molecules entered brain tissues from the circulation. The results of the subacute experiments indicate that the 14C-labelled EGIS-3886, or its metabolite(s) carrying the tracer, reach an equilibrium as early as on the second to third day, whilst the level of 3H-radioactivity continually increases during the six days of repeated administration. In the subacute experiments the peak concentrations were reached at 0.5 h after the final treatment. However, their values for 3H were higher than in acute experiments. The last tendency was not observed in the case of 14C-tracer. The AUC values of 3H-labelled EGIS-3886 determined in subacute experiments predominated over 14C; the ratios were 50 to 60 in all brain regions. The enterohepatic cycle, seen after a single dose, also operated after repeated dosage. The time related concentrations of EGIS-3886 in the hypophysis were at least two times higher than that in the plasma and the brain tissues. No significant difference was seen in the concentrations of EGIS-3886 in the symmetrical (left and right) regions of the brain.
Differential EEG effects of the anxiolytic drugs, Deramciclane (EGIS-3886), ritanserin and chlordiazepoxide in rats
Psychopharmacology (Berl) 1999 Mar;142(3):318-26.PMID:10208325DOI:10.1007/s002130050895.
The influence of serotonergic and benzodiazepine type anxiolytic drugs on the cortical activation and sleep-wakefulness cycle were compared by evaluating the effects of ritanserin and Deramciclane (EGIS-3886), two 5-HT2 receptor antagonists, and chlordiazepoxide on the electroencephalogram (EEG) in freely moving rats. Following drug administration (1, 3, and 10 mg/kg, PO for all drugs), EEG was continuously sampled for 6 h and power spectra were calculated for every 5 s to assess changes in slow wave activity and sleep phases. In a separate test, anticonvulsant effects of the drugs were examined in mice. Both deramciclane and ritanserin slightly increased total time spent in deep sleep (DS) and lengthened sleep episodes. In contrast, chlordiazepoxide had a strong inhibitory action on DS, sleep time being shifted to more superficial light sleep (LS). The incidence and length of the high voltage spindle (HVS) episodes characteristic for the motionless, awake rat were increased at the highest dose of both deramciclane and ritanserin, while it was decreased by chlordiazepoxide. In mice, chlordiazepoxide had a marked anticonvulsant effect, while deramciclane was moderately effective and ritanserin ineffective. In conclusion, the 5-HT2 receptor antagonist anxiolytic drugs seem to be superior compared to the benzodiazepine type anxiolytic drug, chlordiazepoxide, as ritanserin and deramciclane improved sleep quality by increasing sleep episode length and time spent in DS, while chlordiazepoxide enhanced sleep fragmentation and decreased DS.
[Investigation of the physico-chemical properties of Deramciclane (EGIS-3886), a new anxiolytic compound. Ionization and lipophilicity]
Acta Pharm Hung 1999 Jun;69(3):123-7.PMID:10401155doi
Ionization and lipophilicity of deramciclane hydrogenfumarate (EGIS-3886), a novel anxiolytic compound being under clinical trial were investigated. The aqueous pKa value and the octanol/water partition coefficient (logP) have been determined using validated analytical approaches. The favourable pharmacokinetic properties of deramciclane are interpreted on the bases of its ionization capability and extreme high lipophilicity.
Oral, intraperitoneal and intravenous pharmacokinetics of Deramciclane and its N-desmethyl metabolite in the rat
J Pharm Pharmacol 2000 Jan;52(1):47-51.PMID:10716602DOI:10.1211/0022357001773670.
The pharmacokinetic properties of Deramciclane fumarate (EGIS-3886), a new potential anxiolitic agent, and its N-desmethyl metabolite have been investigated in Wistar rats after 10 mgkg(-1) Deramciclane fumarate was administered orally, intraperitoneally or intravenously. A highly sensitive, validated and optimized gas chromatographic method with nitrogen selective detection (GC-NPD) using a solid-phase extraction technique was used to determine plasma levels of the parent compound and its N-desmethyl metabolite. After oral administration the absorption of the parent compound was very fast (t(max) 0.5h). The maximum plasma concentration (C(max)) was detected at 44.9, > or =177.8 and > or =2643.0 ngmL(-1) after oral, intraperitoneal and intravenous administration of Deramciclane, respectively. For the metabolite the respective Cmax values were 32.0, > or =25.4 and 51.0 ngmL(-1). The pharmacokinetic curves of both the parent compound and its metabolite showed enterohepatic recirculation for all administration routes. The biological half-life (tbeta 1/2) for Deramciclane ranged from 3.42 to 5.44 h and for the N-desmethyl metabolite the range was 2.90-5.44 h, after administration of the drug by the three different routes. After intravenous administration AUC0-infinity, of Deramciclane was 29.2- and 5.4-times higher than that observed after oral and intraperitoneal treatment, respectively. These AUC0-infinity ratios were only 2.1- and 1.5-times higher for the metabolite. The absolute bioavailability of Deramciclane in rats was 3.42% after oral and 18.49% after intraperitoneal administration. The comparative pharmacokinetic study of Deramciclane in rat after the different administration routes showed fast absorption. Furthermore, plasma levels were found to be administration route-dependent, low bioavailability of the parent compound indicated an extremely fast and strong first-pass metabolism. The apparent volume of distribution suggested strong tissue binding after administration of the drug by any of the three routes studied.