Tetrahidrodeoksikortikosteron
 | |
| IUPAC ime | |
|---|---|
(3α,5β)-3,21-dihidroksipregnan-20-on | |
| Klinički podaci | |
| Drugs.com | Monografija |
| Identifikatori | |
| CAS broj | 567-03-3  |
| ATC kod | None |
| PubChem | CID 91475 |
| Sinonimi | THDOC |
| Hemijski podaci | |
| Formula | C21H34O3 |
| Molarna masa | 334,493 |
| |
| |
Tetrahidrodeoksikortikosteron (skraćeno THDOC; 3α,21-dihidroksi-5α-pregnan-20-on), koji se takođe naziva alotetrahidrokortikosteron, je endogeni neurosteroid.[1] Sintetiše se iz nadbubrežnog hormona deoksikortikosterona dejstvom dva enzima, 5α-reduktaze tipa I i 3α-hidroksisteroid dehidrogenaze.[2] THDOC je snažan pozitivni alosterični modulator GABAA receptora i ima sedativno, anksiolitičko i antikonvulzivno dejstvo.[3][4][5] Promene u normalnom nivou ovog steroida, posebno tokom trudnoće i menstruacije, mogu biti uključene u neke vrste epilepsije (katamenijalna epilepsija) i predmenstrualni sindrom,[6] kao i stres, anksioznost i depresiju.[7][8][9][10][11]
Osobine
[уреди | уреди извор]Tetrahidrodeoksikortikosteron je organsko jedinjenje, koje sadrži 21 atom ugljenika i ima molekulsku masu od 334,493 Da.
| Osobina | Vrednost |
|---|---|
| Broj akceptora vodonika | 3 |
| Broj donora vodonika | 2 |
| Broj rotacionih veza | 2 |
| Particioni koeficijent[12] (ALogP) | 3,2 |
| Rastvorljivost[13] (logS, log(mol/L)) | -5,0 |
| Polarna površina[14] (PSA, Å2) | 57,5 |
Reference
[уреди | уреди извор]- ^ Hosie AM, Wilkins ME, da Silva HM, Smart TG (новембар 2006). „Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites”. Nature. 444 (7118): 486—9. Bibcode:2006Natur.444..486H. PMID 17108970. S2CID 4382394. doi:10.1038/nature05324.
- ^ Agís-Balboa RC, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, Guidotti A (септембар 2006). „Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis”. Proceedings of the National Academy of Sciences of the United States of America. 103 (39): 14602—7. Bibcode:2006PNAS..10314602A. PMC 1600006
. PMID 16984997. doi:10.1073/pnas.0606544103 .
- ^ Kokate TG, Svensson BE, Rogawski MA (септембар 1994). „Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation”. The Journal of Pharmacology and Experimental Therapeutics. 270 (3): 1223—9. PMID 7932175.
- ^ Reddy DS, Rogawski MA (мај 2002). „Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility”. The Journal of Neuroscience. 22 (9): 3795—805. PMC 6758375 . PMID 11978855. doi:10.1523/JNEUROSCI.22-09-03795.2002.
- ^ Reddy DS (2003). „Pharmacology of endogenous neuroactive steroids”. Critical Reviews in Neurobiology. 15 (3–4): 197—234. PMID 15248811. doi:10.1615/critrevneurobiol.v15.i34.20.
- ^ Tuveri A, Paoletti AM, Orrù M, Melis GB, Marotto MF, Zedda P, et al. (јул 2008). „Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy”. Epilepsia. 49 (7): 1221—9. PMID 18325018. S2CID 23596739. doi:10.1111/j.1528-1167.2008.01555.x .
- ^ Reddy DS (март 2003). „Is there a physiological role for the neurosteroid THDOC in stress-sensitive conditions?”. Trends in Pharmacological Sciences. 24 (3): 103—6. PMID 12628349. doi:10.1016/S0165-6147(03)00023-3.
- ^ Reddy DS (2006). „Physiological role of adrenal deoxycorticosterone-derived neuroactive steroids in stress-sensitive conditions”. Neuroscience. 138 (3): 911—20. PMID 16325348. S2CID 23576732. doi:10.1016/j.neuroscience.2005.10.016.
- ^ Eser D, Romeo E, Baghai TC, di Michele F, Schüle C, Pasini A, et al. (2006). „Neuroactive steroids as modulators of depression and anxiety”. Neuroscience. 138 (3): 1041—8. PMID 16310959. S2CID 12033307. doi:10.1016/j.neuroscience.2005.07.007.
- ^ Eser D, Schüle C, Baghai TC, Romeo E, Rupprecht R (2006). „Neuroactive steroids in depression and anxiety disorders: clinical studies” (PDF). Neuroendocrinology. 84 (4): 244—54. PMID 17159334. S2CID 15711990. doi:10.1159/000097879.
- ^ Maguire J, Mody I (фебруар 2007). „Neurosteroid synthesis-mediated regulation of GABA(A) receptors: relevance to the ovarian cycle and stress”. The Journal of Neuroscience. 27 (9): 2155—62. PMC 6673487 . PMID 17329412. doi:10.1523/JNEUROSCI.4945-06.2007.
- ^ Ghose, A.K.; Viswanadhan V.N. & Wendoloski, J.J. (1998). „Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragment Methods: An Analysis of AlogP and CLogP Methods”. J. Phys. Chem. A. 102: 3762—3772. doi:10.1021/jp980230o.
- ^ Tetko IV, Tanchuk VY, Kasheva TN, Villa AE (2001). „Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices”. Chem Inf. Comput. Sci. 41: 1488—1493. PMID 11749573. doi:10.1021/ci000392t.
- ^ Ertl P.; Rohde B.; Selzer P. (2000). „Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties”. J. Med. Chem. 43: 3714—3717. PMID 11020286. doi:10.1021/jm000942e.
Literatura
[уреди | уреди извор]- Hardman JG, Limbird LE, Gilman AG (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10. изд.). New York: McGraw-Hill. ISBN 0071354697. doi:10.1036/0071422803.
- Thomas L. Lemke; David A. Williams, ур. (2007). Foye's Principles of Medicinal Chemistry (6. изд.). Baltimore: Lippincott Willams & Wilkins. ISBN 0781768799.
