Clinical data
Routes of
ATC code
  • none
Pharmacokinetic data
  • 2-[6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylacetamide
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.216.305 Edit this at Wikidata
Chemical and physical data
Molar mass404.34 g·mol−1
3D model (JSmol)
  • CCCN(CCC)C(=O)Cc1n2cc(Cl)ccc2nc1-c3ccc(Cl)cc3
  • InChI=1S/C21H23Cl2N3O/c1-3-11-25(12-4-2)20(27)13-18-21(15-5-7-16(22)8-6-15)24-19-10-9-17(23)14-26(18)19/h5-10,14H,3-4,11-13H2,1-2H3 checkY

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 It was withdrawn from the French market by 1994 and is not approved for marketing anywhere in the world.[3]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]


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]


In 1995, Alpidem was withdrawn from the market in most of the world following reports of severe liver damage.[12]

See also


  1. ^ a b Zivkovic B, Morel E, Joly D, Perrault G, Sanger DJ, Lloyd KG (May 1990). "Pharmacological and behavioral profile of alpidem as an anxiolytic". Pharmacopsychiatry. 23 Suppl 3: 108–13. doi:10.1055/s-2007-1014545. PMID 1974069.
  2. ^ Sanger DJ, Zivkovic B (January 1994). "Discriminative stimulus effects of alpidem, a new imidazopyridine anxiolytic". Psychopharmacology. 113 (3–4): 395–403. doi:10.1007/bf02245215. PMID 7862851. S2CID 24375542.
  3. ^ WHO Drug Information Vol. 8, No. 2, 1994, page 64
  4. ^ Bourguignon JJ (1993). "Endogenous and Synthetic Ligand of Mitochondrial Benzodiazepine Receptors: Structure-Affinity Relationships.". In Giesen-Crouse E (ed.). Peripheral Benzodiazepine Receptors. London: Academic Press. pp. 59–85.
  5. ^ Costa E, Romeo E, Auta J, Papadopoulos V, Kozikowski A, Guidotti A (1991). "Is There a Pharmacology of Brain Steroidogenesis? In Neurosteroid and Brain Function". In Costa E, Paul SM (eds.). Fidia ResearchFundation Symposium Series. New York: Thieme Medical Publisher, Inc. pp. 171–176.
  6. ^ Romeo E, Auta J, Kozikowski AP, Ma D, Papadopoulos V, Puia G, et al. (September 1992). "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. PMID 1326631.
  7. ^ Kozikowski AP, Ma D, Romeo E, Auta J, Papadopoulos V, Puia G, Costa E, Guidotti A (August 1992). "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. doi:10.1002/anie.199210601.
  8. ^ Diamond BI, Nguyen H, O'Neal E, Ochs R, Kaffeman M, Borison RL (1991). "A comparative study of alpidem, a nonbenzodiazepine, and lorazepam in patients with nonpsychotic anxiety". Psychopharmacology Bulletin. 27 (1): 67–71. PMID 1677774.
  9. ^ Kunovac JL, Stahl SM (December 1995). "Future directions in anxiolytic pharmacotherapy". The Psychiatric Clinics of North America. 18 (4): 895–909. doi:10.1016/S0193-953X(18)30030-3. PMID 8748388.
  10. ^ Morton S, Lader M (May 1990). "Studies with alpidem in normal volunteers and anxious patients". Pharmacopsychiatry. 23 Suppl 3: 120–3. doi:10.1055/s-2007-1014547. PMID 1974071.
  11. ^ Frattola L, Garreau M, Piolti R, Bassi S, Albizzati MG, Borghi C, Morselli PL (July 1994). "Comparison of the efficacy, safety and withdrawal of alpidem and alprazolam in anxious patients". The British Journal of Psychiatry. 165 (1): 94–100. doi:10.1192/bjp.165.1.94. PMID 7802852. S2CID 45424355.
  12. ^ Berson A, Descatoire V, Sutton A, Fau D, Maulny B, Vadrot N, et al. (November 2001). "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. PMID 11602696.