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Clinical data
Synonyms Antalarmin
ATC code
  • none
Legal status
Legal status
  • In general: legal
CAS Number
PubChem CID
Chemical and physical data
Formula C24H34N4
Molar mass 378.55 g/mol
3D model (JSmol)

Antalarmin is a drug that acts as a CRF-1 antagonist.

Corticotropin-releasing factor (CRF), also known as Corticotropin-releasing hormone, is an endogenous peptide hormone released in response to various triggers such as chronic stress and drug addiction. This, then, triggers the release of corticotropin (ACTH), another hormone involved in the physiological response to stress. Chronic release of CRF and ACTH is believed to be directly or indirectly involved in many of the harmful physiological effects of chronic stress, such as excessive glucocorticoid release, stomach ulcers, anxiety, diabetes mellitus, osteoporosis, depression, and development of high blood pressure and consequent cardiovascular problems.[1]

Antalarmin is a non-peptide drug that blocks the CRF-1 receptor, and, as a consequence, reduces the release of ACTH in response to chronic stress.[2] This has been demonstrated in animals to reduce the behavioural responses to stressful situations,[3] and it is proposed that antalarmin itself, or more likely newer CRF antagonist drugs still under development,[4] could be useful for reducing the adverse health consequences of chronic stress in humans, as well as having possible uses in the treatment of conditions such as anxiety, depression, and drug addiction.[5]

Results so far have had limited success, with various CRF antagonists being tested, which showed some antidepressant effects, but failed to produce an effect comparable with conventional antidepressant drugs.[6] However more positive results were seen when antalarmin was combined with an SSRI antidepressant, suggesting a potential for synergistic effect.[7] Encouraging results have also been observed using antalarmin as a potential treatment for anxiety[8][9] and stress-induced hypertension.[10]

Chronic antalarmin treatment also showed anti-inflammatory effects and has been suggested as having potential uses in the treatment of inflammatory conditions such as arthritis,[11] as well as stress-induced gastrointestinal ulcers[12] and irritable bowel syndrome.[13][14]

Mixed results have been seen in research into the use of antalarmin and other CRF-1 antagonists in the treatment of drug addiction disorders. Tests of antalarmin on cocaine use in cocaine-addicted monkeys produced only slight reductions of use that were not statistically significant,[15] however in tests on cocaine-addicted rats, antalarmin did prevent dose escalation with prolonged use, suggesting that it might stabilise cocaine use and prevent it increasing over time, although without consistently reducing it.[16]

Antalarmin also showed positive effects in reducing withdrawal syndrome from chronic opioid use,[17] and significantly reduced self-administration of ethanol in ethanol-addicted rodents.[18][19][20]

See also[edit]


  1. ^ Zoumakis, E; Rice, K. C; Gold, P.W; Chrousos, G. P (2006). "Potential Uses of Corticotropin-Releasing Hormone Antagonists". Annals of the New York Academy of Sciences. 1083: 239–51. Bibcode:2006NYASA1083..239Z. doi:10.1196/annals.1367.021. PMID 17148743. 
  2. ^ Webster, E L; Lewis, D B; Torpy, D J; Zachman, E K; Rice, K C; Chrousos, G P (1996). "In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: Suppression of pituitary ACTH release and peripheral inflammation". Endocrinology. 137 (12): 5747–50. doi:10.1210/endo.137.12.8940412. PMID 8940412. 
  3. ^ Deak, Terrence; Nguyen, Kien T.; Ehrlich, Andrea L.; Watkins, Linda R.; Spencer, Robert L.; Maier, Steven F.; Licinio, Julio; Wong, Ma-Li; Chrousos, George P.; Webster, Elizabeth; Gold, Philip W. (1999). "The Impact of the Nonpeptide Corticotropin-Releasing Hormone Antagonist Antalarmin on Behavioral and Endocrine Responses to Stress1". Endocrinology. 140 (1): 79–86. doi:10.1210/endo.140.1.6415. PMID 9886810. 
  4. ^ Nielsen, Darci M.; Carey, Galen J.; Gold, Lisa H. (2004). "Antidepressant-like activity of corticotropin-releasing factor type-1 receptor antagonists in mice". European Journal of Pharmacology. 499 (1–2): 135–46. doi:10.1016/j.ejphar.2004.07.091. PMID 15363960. 
  5. ^ McCarthy, J. R.; Heinrichs, S. C.; Grigoriadis, D. E. (1999). "Recent advances with the CRF1 receptor: Design of small molecule inhibitors, receptor subtypes and clinical indications". Current Pharmaceutical Design. 5 (5): 289–315. PMID 10213797. 
  6. ^ Jutkiewicz, Emily M.; Wood, Susan K.; Houshyar, Hani; Hsin, Ling-Wei; Rice, Kenner C.; Woods, James H. (2005). "The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats". Psychopharmacology. 180 (2): 215–23. doi:10.1007/s00213-005-2164-z. PMC 1315297Freely accessible. PMID 15696320. 
  7. ^ Ducottet, Cecile; Griebel, Guy; Belzung, Catherine (2003). "Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 27 (4): 625–31. doi:10.1016/S0278-5846(03)00051-4. PMID 12787849. 
  8. ^ Zorrilla, Eric P; Valdez, Glenn R; Nozulak, Joachim; Koob, George F; Markou, Athina (2002). "Effects of antalarmin, a CRF type 1 receptor antagonist, on anxiety-like behavior and motor activation in the rat". Brain Research. 952 (2): 188–99. doi:10.1016/S0006-8993(02)03189-X. PMID 12376179. 
  9. ^ Habib, K. E.; Weld, K. P.; Rice, K. C.; Pushkas, J.; Champoux, M.; Listwak, S.; Webster, E. L.; Atkinson, A. J.; Schulkin, J.; Contoreggi, C.; Chrousos, G. P.; McCann, S. M.; Suomi, S. J.; Higley, J. D.; Gold, P. W. (2000). "Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates". Proceedings of the National Academy of Sciences. 97 (11): 6079–84. Bibcode:2000PNAS...97.6079H. doi:10.1073/pnas.97.11.6079. PMC 18561Freely accessible. PMID 10823952. 
  10. ^ Briscoe, Richard J.; Cabrera, Camilo L.; Baird, Theodore J.; Rice, Kenner C.; Woods, James H. (2000). "Antalarmin blockade of corticotropin releasing hormone-induced hypertension in rats". Brain Research. 881 (2): 204–7. doi:10.1016/S0006-8993(00)02742-6. PMID 11036160. 
  11. ^ Webster, E. L.; Barrientos, R. M.; Contoreggi, C; Isaac, M. G.; Ligier, S; Gabry, K. E.; Chrousos, G. P.; McCarthy, E. F.; Rice, K. C.; Gold, P. W.; Sternberg, E. M. (2002). "Corticotropin releasing hormone (CRH) antagonist attenuates adjuvant induced arthritis: Role of CRH in peripheral inflammation". The Journal of rheumatology. 29 (6): 1252–61. PMID 12064844. 
  12. ^ Gabry, K E; Chrousos, G P; Rice, K C; Mostafa, R M; Sternberg, E; Negrao, A B; Webster, E L; McCann, S M; Gold, P W (2002). "Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs". Molecular Psychiatry. 7 (5): 474–83, 433. doi:10.1038/ PMID 12082565. 
  13. ^ Greenwood-Van Meerveld, b.; Johnson, a. c.; Cochrane, s.; Schulkin, j.; Myers, d. a. (2005). "Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats". Neurogastroenterology and Motility. 17 (3): 415–22. doi:10.1111/j.1365-2982.2005.00648.x. PMID 15916629. 
  14. ^ Martinez, V.; Tache, Y. (2006). "CRF1 Receptors as a Therapeutic Target for Irritable Bowel Syndrome". Current Pharmaceutical Design. 12 (31): 4071–88. doi:10.2174/138161206778743637. PMID 17100612. 
  15. ^ Mello, Nancy K.; Negus, S. Stevens; Rice, Kenner C.; Mendelson, Jack H. (2006). "Effects of the CRF1 antagonist antalarmin on cocaine self-administration and discrimination in rhesus monkeys". Pharmacology Biochemistry and Behavior. 85 (4): 744–51. doi:10.1016/j.pbb.2006.11.008. PMID 17182090. 
  16. ^ Specio, Sheila E.; Wee, Sunmee; o'Dell, Laura E.; Boutrel, Benjamin; Zorrilla, Eric P.; Koob, George F. (2007). "CRF1 receptor antagonists attenuate escalated cocaine self-administration in rats". Psychopharmacology. 196 (3): 473–82. doi:10.1007/s00213-007-0983-9. PMC 2769571Freely accessible. PMID 17965976. 
  17. ^ Stinus, Luis; Cador, Martine; Zorrilla, Eric P; Koob, George F (2004). "Buprenorphine and a CRF1 Antagonist Block the Acquisition of Opiate Withdrawal-Induced Conditioned Place Aversion in Rats". Neuropsychopharmacology. 30 (1): 90–8. doi:10.1038/sj.npp.1300487. PMID 15138444. 
  18. ^ Funk, Cindy K.; Zorrilla, Eric P.; Lee, Mei-Jing; Rice, Kenner C.; Koob, George F. (2007). "Corticotropin-Releasing Factor 1 Antagonists Selectively Reduce Ethanol Self-Administration in Ethanol-Dependent Rats". Biological Psychiatry. 61 (1): 78–86. doi:10.1016/j.biopsych.2006.03.063. PMC 2741496Freely accessible. PMID 16876134. 
  19. ^ Chu, Kathleen; Koob, George F.; Cole, Maury; Zorrilla, Eric P.; Roberts, Amanda J. (2007). "Dependence-induced increases in ethanol self-administration in mice are blocked by the CRF1 receptor antagonist antalarmin and by CRF1 receptor knockout". Pharmacology Biochemistry and Behavior. 86 (4): 813–21. doi:10.1016/j.pbb.2007.03.009. PMC 2170886Freely accessible. PMID 17482248. 
  20. ^ Marinelli, Peter W.; Funk, Douglas; Juzytsch, Walter; Harding, Stephen; Rice, Kenner C.; Shaham, Yavin; Lê, A. D. (2007). "The CRF1 receptor antagonist antalarmin attenuates yohimbine-induced increases in operant alcohol self-administration and reinstatement of alcohol seeking in rats". Psychopharmacology. 195 (3): 345–55. doi:10.1007/s00213-007-0905-x. PMID 17705061.