Alpidem
(Synonyms: 阿尔吡登,Ananxyl) 目录号 : GC49199
An anxiolytic agent
Cas No.:82626-01-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Alpidem is an anxiolytic agent.1 It selectively binds to α1β2γ2 subunit-containing GABAA receptors over α5β2γ2 subunit-containing GABAA receptors in HEK293 cells (IC50s = 0.017 and ≥10 µM, respectively, for the recombinant rat receptors).2 Alpidem also binds to the GABAA/benzodiazepine receptor complex and translocator protein 18 kDa (TSPO) with IC50 values of 0.028 and 0.0079 µM, respectively.3 It reduces marble burying in mice, indicating anxiolytic activity, with a minimum effective dose (MED) of 10 mg/kg.4 Unlike the benzodiazepine alprazolam, alpidem does not induce sedation in mice when administered at doses up to 2 mg/kg.5 Formulations containing alpidem have previously been used in the treatment of generalized anxiety disorder.
1.Skolnick, P.Anxioselective anxiolytics: On a quest for the holy grailTrends Pharamacol. Sci.33(11)611-620(2012) 2.Faure-Halley, C., Graham, D., Arbilla, S., et al.Expression and properties of recombinant α1β2γ2 and α5β2γ2 forms of the rat GABAA receptorEur. J. Pharmacol.246(3)283-287(1993) 3.Trapani, G., Franco, M.C., Ricciardi, L., et al.Synthesis and binding affinity of 2-phenylimidazo[1,2-alpha]pyridine derivatives for both central and peripheral benzodiazepine receptors. A new series of high-affinity and selective ligands for the peripheral typeJ. Med. Chem.40(19)3109-3118(1997) 4.Zivkovic, B., Morel, E., Joly, D., et al.Pharmacological and behavioral profile of alpidem as an anxiolyticPharmacopsychiatry23(Suppl. 3)108-113(1990) 5.HascoËt, M., and Bourin, M.Anticonflict effect of alpidem as compared with the benzodiazepine alprazolam in ratsPharmacol. Biochem. Behav.56(2)317-324(1997)
| Cas No. | 82626-01-5 | SDF | |
| 别名 | 阿尔吡登,Ananxyl | ||
| Canonical SMILES | O=C(CC1=C(C2=CC=C(C=C2)Cl)N=C3C=CC(Cl)=CN31)N(CCC)CCC | ||
| 分子式 | C21H23Cl2N3O | 分子量 | 404.3 |
| 溶解度 | DMSO : 25 mg/mL (61.83 mM; Need ultrasonic) | 储存条件 | -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4734 mL | 12.3671 mL | 24.7341 mL |
| 5 mM | 0.4947 mL | 2.4734 mL | 4.9468 mL |
| 10 mM | 0.2473 mL | 1.2367 mL | 2.4734 mL |
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Pharmacological and behavioral profile of Alpidem as an anxiolytic
Pharmacopsychiatry 1990 May;23 Suppl 3:108-13.PMID:1974069DOI:10.1055/s-2007-1014545.
Pharmacological and behavioral studies in mice and rats have shown that the imidazopyridine Alpidem possesses anxiolytic activity with a profile which is substantially different from that of benzodiazepines. Thus, in mice, Alpidem inhibited marble-burying behavior and enhanced feeding under stressful conditions, as did benzodiazepines; in contrast to these drugs, however, Alpidem was inactive against shock-induced fighting and shock-suppressed exploration. In rats, Alpidem exerted anticonflict activity in the punished drinking test, but failed to antagonize punishment-induced inhibition of operant behavior. Moreover, in rats trained to discriminate chlordiazepoxide from saline, Alpidem did not produce a benzodiazepine-like interoceptive stimulus. Alpidem also produced anticonvulsant effects in a variety of tests sensitive to benzodiazepines. However, the order of potencies against convulsions induced by different convulsive agents was different from that of the benzodiazepines. Alpidem decreased motor performance in the rotarod test and only produced a deficit in muscle strength at doses which were more than 20 times higher than the doses active in anxiolytic tests. Moreover, Alpidem did not interfere with the acquisition of conditioned fear, except at very high doses, indicating a weak potential to impair memory. The effects of Alpidem were antagonized by flumazenil, indicating that central omega receptors are involved in the action of this drug. The weak sedative effects of Alpidem may be attributed to its low intrinsic activity, as demonstrated by its low efficacy in increasing latency to isoniazid-induced convulsions.
Alpidem and psychological performance in elderly subjects
Pharmacopsychiatry 1990 May;23 Suppl 3:124-8.PMID:1974072DOI:10.1055/s-2007-1014548.
With increasing age there is a concurrent increase in the side effects following psychotropic medication. The necessity of measuring the magnitude of the extent of the side effects using a properly constructed psychometric test battery is illustrated with reference to a dose ranging study compared to acute dose effects of 25, 50 and 100 mg Alpidem in a population of elderly volunteers. The study was both placebo and verum (lorazepam 2 mg) controlled and the treatments were administered according to a crossover design with each subject acting as their own control. The effects of the verum were evident on all the tests and under these conditions there was no effect on psychological differences following doses of 25 and 50 mg Alpidem. There was an initial deterioration one hour after dosing following 100 mg Alpidem which was readily attenuated by three hours. No differences with any of the doses of Alpidem were able to be detected at any other time point even though the verum continued to show the sensitivity of the battery to tests to sedative amnestic sensori-motor and information processing activities.
Studies with Alpidem in normal volunteers and anxious patients
Pharmacopsychiatry 1990 May;23 Suppl 3:120-3.PMID:1974071DOI:10.1055/s-2007-1014547.
Alpidem, an imidazo-pyridine compound, has been evaluated as an anxiolytic in comparison with placebo and lorazepam. In the first of our normal volunteer studies, we compared single doses of Alpidem, 25, 50 and 100 mg with lorazepam 2 mg and placebo on a range of cognitive, psychomotor and EEG variables. Lorazepam and the highest (100 mg) dose of Alpidem impaired performance on a range of psychomotor tasks, the effects of the benzodiazepine being more severe and more prolonged. No impairment of performance was observed with the 25 and 50 mg doses. In the second study, the focus was on memory functions. Lorazepam, 2 mg, caused anterograde amnesia which was most apparent 1 h post-drug but persisted until 4 h: sedation was marked. By contrast, single doses (25, 50 mg) of Alpidem had little effect on either memory or alertness. The third study compared the effects of Alpidem (25, 50 mg) and lorazepam (1 mg) with placebo, each given twice-daily for 8 days to normal volunteers. On the final day, a test dose of ethanol was given. Lorazepam impaired many tests of cognitive and psychomotor function, and this impairment was enhanced by ethanol. By contrast, Alpidem produced less impairment with less interaction with alcohol. In a fourth, clinical, study, 24 patients with a DSM III primary diagnosis of generalised anxiety disorder were treated, under double blind conditions, with doses adjusted according to clinical need of either Alpidem 25-150 mg daily or lorazepam 1-6 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users
Cochrane Database Syst Rev 2018 Mar 15;3(3):CD011481.PMID:29543325DOI:10.1002/14651858.CD011481.pub2.
Background: Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering. Objectives: To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use. Search methods: We searched the following electronic databases up to October 2017: Cochrane Drugs and Alcohol Group's Specialised Register of Trials, CENTRAL, PubMed, Embase, CINAHL, and ISI Web of Science. We also searched ClinicalTrials.gov, the WHO ICTRP, and ISRCTN registry, and checked the reference lists of included studies for further references to relevant randomised controlled trials. Selection criteria: We included randomised controlled trials comparing pharmacological treatment versus placebo or no intervention or versus another pharmacological intervention in adults who had been treated with benzodiazepines for at least two months and/or fulfilled criteria for benzodiazepine dependence (any criteria). Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: We included 38 trials (involving 2543 participants), but we could only extract data from 35 trials with 2295 participants. Many different interventions were studied, and no single intervention was assessed in more than four trials. We extracted data on 18 different comparisons. The risk of bias was high in all trials but one. Trial Sequential Analysis showed imprecision for all comparisons.For benzodiazepine discontinuation, we found a potential benefit of valproate at end of intervention (1 study, 27 participants; risk ratio (RR) 2.55, 95% confidence interval (CI) 1.08 to 6.03; very low-quality evidence) and of tricyclic antidepressants at longest follow-up (1 study, 47 participants; RR 2.20, 95% CI 1.27 to 3.82; low-quality evidence).We found potentially positive effects on benzodiazepine withdrawal symptoms of pregabalin (1 study, 106 participants; mean difference (MD) -3.10 points, 95% CI -3.51 to -2.69; very low-quality evidence), captodiame (1 study, 81 participants; MD -1.00 points, 95% CI -1.13 to -0.87; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -3.57 points, 95% CI -5.34 to -1.80; very low-quality evidence), tricyclic antidepressants (1 study, 38 participants; MD -19.78 points, 95% CI -20.25 to -19.31; very low-quality evidence), and flumazenil (3 studies, 58 participants; standardised mean difference -0.95, 95% CI -1.71 to -0.19; very low-quality evidence) at end of intervention. However, the positive effect of paroxetine on benzodiazepine withdrawal symptoms did not persist until longest follow-up (1 study, 54 participants; MD -0.13 points, 95% CI -4.03 to 3.77; very low-quality evidence).The following pharmacological interventions reduced symptoms of anxiety at end of intervention: carbamazepine (1 study, 36 participants; MD -6.00 points, 95% CI -9.58 to -2.42; very low-quality evidence), pregabalin (1 study, 106 participants; MD -4.80 points, 95% CI -5.28 to -4.32; very low-quality evidence), captodiame (1 study, 81 participants; MD -5.70 points, 95% CI -6.05 to -5.35; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -6.75 points, 95% CI -9.64 to -3.86; very low-quality evidence), and flumazenil (1 study, 18 participants; MD -1.30 points, 95% CI -2.28 to -0.32; very low-quality evidence).Two pharmacological treatments seemed to reduce the proportion of participants that relapsed to benzodiazepine use: valproate (1 study, 27 participants; RR 0.31, 95% CI 0.11 to 0.90; very low-quality evidence) and cyamemazine (1 study, 124 participants; RR 0.33, 95% CI 0.14 to 0.78; very low-quality evidence). Alpidem decreased the proportion of participants with benzodiazepine discontinuation (1 study, 25 participants; RR 0.41, 95% CI 0.17 to 0.99; number needed to treat for an additional harmful outcome (NNTH) 2.3 participants; low-quality evidence) and increased the occurrence of withdrawal syndrome (1 study, 145 participants; RR 4.86, 95% CI 1.12 to 21.14; NNTH 5.9 participants; low-quality evidence). Likewise, magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines (1 study, 144 participants; RR 0.80, 95% CI 0.66 to 0.96; NNTH 5.8; very low-quality evidence).Generally, adverse events were insufficiently reported. Specifically, one of the flumazenil trials was discontinued due to severe panic reactions. Authors' conclusions: Given the low or very low quality of the evidence for the reported outcomes, and the small number of trials identified with a limited number of participants for each comparison, it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users. Due to poor reporting, adverse events could not be reliably assessed across trials. More randomised controlled trials are required with less risk of systematic errors ('bias') and of random errors ('play of chance') and better and full reporting of patient-centred and long-term clinical outcomes. Such trials ought to be conducted independently of industry involvement.
On the therapeutic action of Alpidem in anxiety disorders: an overview of the European data
Pharmacopsychiatry 1990 May;23 Suppl 3:129-34.PMID:1974073DOI:10.1055/s-2007-1014549.
This review analyzes the available data on the therapeutic activity of Alpidem in various anxiety syndromes. Up to now, 17 studies have been completed in Europe, dealing with a total population of more than 1500 patients suffering from either chronic (n = 987) or situational anxiety (n = 400). In a series of five placebo-controlled double-blind studies in situations of stress-induced anxiety (gastroscopy, minor surgery, cardiac catheterization), the therapeutic efficacy of Alpidem was evident in 53% of the patients and significantly (P less than 0.001) superior to that of placebo (30%). In more than 400 patients suffering from generalized anxiety or adjustment disorders with anxious mood, six double-blind studies run against placebo or reference drug over a period of two to three weeks indicated an anxiolytic effect superior (P less than 0.01) to that of placebo and comparable to that of reference drugs (DZ, LZP, CZP). A long-term (6-12 months) open-label study conducted on a population of more than 300 patients suffering from chronic anxiety indicated that no tachyphylaxis occurs during prolonged treatment and that following abrupt drug discontinuation no withdrawal or rebound phenomena are observed. Globally, Alpidem appears to be well tolerated with a minimum of dose-related, sedative effects (6-7% of the cases) and no effects on memory or cognitive functions. Four studies conducted specifically in an elderly population (n = 191) indicate that the elderly patients do not show an increased sensitivity to Alpidem. On the contrary, as in adults, the anxiolytic effect was not accompanied by a reduction in performance or in cognitive functions nor by withdrawal reactions when treatment was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)