Chemistry:Alpidem
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| Routes of administration | Oral |
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| Excretion | Renal |
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| Formula | C21H23Cl2N3O |
| Molar mass | 404.34 g·mol−1 |
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Alpidem (Ananxyl) is an anxiolytic drug from the imidazopyridine family, related to the more well known sleeping medication zolpidem. Unlike zolpidem however, alpidem does not produce sedative effects at normal doses, and is instead used specifically for the treatment of anxiety.[1][2]
Alpidem was developed by Synthélabo (now part of Sanofi-Aventis). It was approved for marketing in France in 1991. Clinical trials to obtain US FDA approval were halted in 1992 and the drug never received FDA approval. It was withdrawn from the French market by 1994 and is not approved for marketing anywhere in the world.[3]
Alpidem has nanomolar binding affinity for both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor (PBR) (translocator protein 18 kDa) (PBR (Ki ) 0.5-7 nM) and CBR (Ki ) 1-28 nM, respectively).[4][5][6][7] However, the chemical structure of alpidem is not related to that of the benzodiazepines, and alpidem is thus sometimes referred to as a nonbenzodiazepine.[8]
Indications
Alpidem is not approved for any indication.
Use prior to removal from market
Alpidem was generally prescribed to patients with moderate to severe anxiety.[9] Most of these patients had exhibited either sensitivity or resistance to benzodiazepine therapy, and therefore switched to a non-benzodiazepine medication due to the reduced incidence of side effects relative to benzodiazepine drugs.[10][11] Alpidem produced little or no sedative or hypnotic action at normal doses, but may have produced sedation when used at a high dose, and only had anticonvulsant actions at much higher doses than those used clinically for the treatment of anxiety.[1]
Dangers
In 1995, Alpidem was withdrawn from the market in most of the world following reports of severe liver damage.[12]
See also
References
- ↑ 1.0 1.1 "Pharmacological and behavioral profile of alpidem as an anxiolytic". Pharmacopsychiatry 23 Suppl 3: 108–13. May 1990. doi:10.1055/s-2007-1014545. PMID 1974069.
- ↑ "Discriminative stimulus effects of alpidem, a new imidazopyridine anxiolytic". Psychopharmacology 113 (3–4): 395–403. January 1994. doi:10.1007/bf02245215. PMID 7862851.
- ↑ WHO Drug Information Vol. 8, No. 2, 1994, page 64
- ↑ "Endogenous and Synthetic Ligand of Mitochondrial Benzodiazepine Receptors: Structure-Affinity Relationships.". Peripheral Benzodiazepine Receptors. London: Academic Press. 1993. pp. 59–85.
- ↑ "Is There a Pharmacology of Brain Steroidogenesis? In Neurosteroid and Brain Function". Fidia ResearchFundation Symposium Series. New York: Thieme Medical Publisher, Inc.. 1991. pp. 171–176.
- ↑ "2-Aryl-3-indoleacetamides (FGIN-1): a new class of potent and specific ligands for the mitochondrial DBI receptor (MDR)". The Journal of Pharmacology and Experimental Therapeutics 262 (3): 971–8. September 1992. PMID 1326631.
- ↑ "Synthesis of (2‐Arylindol‐3‐yl) acetamides as Probes of Mitochondrial Steroidogenesis—A New Mechanism for GABAA Receptor Modulation.". Angewandte Chemie International Edition in English 31 (8): 1060–2. August 1992. doi:10.1002/anie.199210601.
- ↑ "A comparative study of alpidem, a nonbenzodiazepine, and lorazepam in patients with nonpsychotic anxiety". Psychopharmacology Bulletin 27 (1): 67–71. 1991. PMID 1677774.
- ↑ "Future directions in anxiolytic pharmacotherapy". The Psychiatric Clinics of North America 18 (4): 895–909. December 1995. doi:10.1016/S0193-953X(18)30030-3. PMID 8748388.
- ↑ "Studies with alpidem in normal volunteers and anxious patients". Pharmacopsychiatry 23 Suppl 3: 120–3. May 1990. doi:10.1055/s-2007-1014547. PMID 1974071.
- ↑ "Comparison of the efficacy, safety and withdrawal of alpidem and alprazolam in anxious patients". The British Journal of Psychiatry 165 (1): 94–100. July 1994. doi:10.1192/bjp.165.1.94. PMID 7802852.
- ↑ "Toxicity of alpidem, a peripheral benzodiazepine receptor ligand, but not zolpidem, in rat hepatocytes: role of mitochondrial permeability transition and metabolic activation". The Journal of Pharmacology and Experimental Therapeutics 299 (2): 793–800. November 2001. PMID 11602696.
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