Antalarmin
| |||
| (IUPAC) ime | |||
|---|---|---|---|
| N-butyl-N-ethyl-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[3,2-e]pyrimidin-4-amine | |||
| Klinički podaci | |||
| Identifikatori | |||
| CAS broj | 157284-96-3 | ||
| ATC kod | nije dodeljen | ||
| PubChem[1][2] | 177990 | ||
| ChemSpider[3] | 154945 | ||
| ChEMBL[4] | CHEMBL296641 
| ||
| Hemijski podaci | |||
| Formula | C24H34N4 | ||
| Mol. masa | 378.55 g/mol | ||
| SMILES | eMolekuli & PubHem | ||
| |||
| Sinonimi | Antalarmin | ||
| Farmakoinformacioni podaci | |||
| Trudnoća | ? | ||
| Pravni status | Legal | ||
Antalarmin je lek koji deluje kao antagonist kortikotropin-oslobađajućeg hormonskog receptora 1.
Kortikotropin-oslobađajući faktor (CRF), takođe poznat kao kortikotropin-oslobađajući hormon, je endogeni peptidni hormon oslobođen u responsu na razne stimuluse kao što su hronični stres i adikcija na droge. To zatim inicira oslobađanje kortikotropina (ACTH), hormona koji učestvuje u fiziološkom responsu na stres. Smatra se da hronično oslobađanje CRF i ACTH hormona direktno ili indirektno učestvuje u mnogim štetnim fiziološkim efektima hroničnog stresa, kao što su eksesivno oslobađanje glukokortikoida, dijabetes melitus, osteoporoza, čir na dvanaestopalačnom crevu, anksioznost, depresija, i razvoj visokog krvnog pritiska i konsekventni kardiovaskularni problemi.[5]
Antalarmin je nepeptidni lek koji blokira CRF-1 receptor, i kao posledica toga, umanjuje oslobađanje ACTH-a u responsu na hronični stres.[6] Na životinjskim studijama je pokazano da redukuje response na stresne situacije,[7] i stoga se smatra da antalarmin, ili noviji CRF antagonisti u razvoju,[8] mogu da budu korisni u umanjenju nepoželjnih zdravstvenih posledica hroničnog stresa kod ljudi, i da imaju potencijal za primenu u lečenju anksioznosti, depresije, i adikcije na droge.[9]
Rezultati do sada sprovedenih ispitivanja su prilično ograničeni. Neki od CRF antagonista su pokazali antidepresivno dejstvo, ali oni nije uporedivo sa konvencijalnim antidepresivima.[10] Pozitivniji rezultatu su zabeleženi kad se antalarmin koristi u kombinaciji sa SSRI antidepresivima, što sugerira postojanje potencijalnog sinergističkog dejstva.[11] Ohrabrujući rezultati su takođe nađeni u primeni antalarmina kao potencijalnog leka za anksioznost[12][13] i stresom indukovanu hipertenziju.[14]
- ↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519.
- ↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
- ↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846.
- ↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594.
- ↑ Zoumakis E, Rice KC, Gold PW, Chrousos GP. Potential uses of corticotropin-releasing hormone antagonists. Annals of the New York Academy of Sciences. 2006 Nov;1083:239-51.
- ↑ Webster EL, Lewis DB, Torpy DJ, Zachman EK, Rice KC, Chrousos GP. 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. 1996 Dec;137(12):5747-50.
- ↑ Deak T, Nguyen KT, Ehrlich AL, Watkins LR, Spencer RL, Maier SF, Licinio J, Wong ML, Chrousos GP, Webster E, Gold PW. The impact of the nonpeptide corticotropin-releasing hormone antagonist antalarmin on behavioral and endocrine responses to stress. Endocrinology. 1999 Jan;140(1):79-86.
- ↑ Nielsen DM, Carey GJ, Gold LH. Antidepressant-like activity of corticotropin-releasing factor type-1 receptor antagonists in mice. European Journal of Pharmacology. 2004 Sep 19;499(1-2):135-46.
- ↑ McCarthy JR, Heinrichs SC, Grigoriadis DE. Recent advances with the CRF1 receptor: design of small molecule inhibitors, receptor subtypes and clinical indications. Current Pharmaceutical Design. 1999 May;5(5):289-315.
- ↑ Jutkiewicz EM, Wood SK, Woods JH. 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 (Berlin). 2005 July; 180(2): 215–223.
- ↑ Ducottet C, Griebel G, Belzung C. Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice. Progress in Neuropsychopharmacology and Biological Psychiatry. 2003 Jun;27(4):625-31.
- ↑ Zorrilla EP, Valdez GR, Nozulak J, Koob GF, Markou A. Effects of antalarmin, a CRF type 1 receptor antagonist, on anxiety-like behavior and motor activation in the rat. Brain Research. 2002 Oct 18;952(2):188-99.
- ↑ Habib KE, Weld KP, Rice KC, Pushkas J, Champoux M, Listwak S, Webster EL, Atkinson AJ, Schulkin J, Contoreggi C, Chrousos GP, McCann SM, Suomi SJ, Higley JD, Gold PW. 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 USA. 2000 May 23;97(11):6079-84.
- ↑ Briscoe RJ, Cabrera CL, Baird TJ, Rice KC, Woods JH. Antalarmin blockade of corticotropin releasing hormone-induced hypertension in rats. Brain Research. 2000 Oct 27;881(2):204-7.
