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Ergolin

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Ergolin
Naziv lijekaErgolin
GrupaAlkaloidi
Klasifikacija
CAS registarski broj478-88-6
Dostupnost bez recepta: Djelimično
Stručne informacije
Hemijske osobine

Ime po IUPAC ---
Sumarna formulaC14H16N2
Farmakokinetičke osobine
Izlučivanje
PubChem: 6857537

Ergolin je osnovna struktura mnogih alkaloida i njihovih sintetičkih derivata. Alkaloidi ergolina su prvi put okarakterisani u ergotu. Neki od njih su povezani sa stanjem ergotizma, koji može poprimiti konvulzivni oblik.[1]“Smatra se da klavini značajno doprinose konvulzivnom ergotizmu, budući da ergoti C. fusiformis, koji posjeduju klavine, ali ne i [lizerginsku kiselinu] ili lizergil amide, uzrokuju konvulzivne simptome (26). Međutim, poznato je da ergopeptini proizvode slične simptome, a smatra se da uzrokuju i gangrenozni ergotizam (6). Pojava konvulzivnog ergotizma bez suhe gangrene sugerira da su uključeni drugi klavinski ili lizergilni alkaloidi ili da pojedinačni efekti specifičnih ergopeptina mogu dati klinički različite sindrome („6“).”
II. Kroz vijekove: Historija upotrebe, zloupotrebe i trovanja ergot alkaloida ili gangrenozni oblik. Uprkos tome, mnogi ergolinski alkaloidi pokazali su se klinički korisnima. Godišnja svjetska proizvodnja ergot alkaloida procijenjena je na 5.000–8.000 kg svih ergopeptina i 10.000–15.000 kg lizerginske kiseline, koja se prvenstveno koristi u proizvodnji polusintetskih derivata.[2]

Drugi, kao što su dietilamid lizerginske kiseline, poznatiji kao LSD, polusintetski derivat, i ergin, prirodni derivat koji se nalazi u Argyreia nervosa, Ipomoea tricolor i srodnim poznatim vrstama.

Prirodno pojavljivanje

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Ergolinski alkaloidi se nalaze u gljivama kao što su Claviceps purpurea, Claviceps paspali,[3] |quote =
“Whereas ergine, lysergic acid hydroxyethylamide, and lysergyl L-valine methylester occur in ergot of rye only in trace amounts, ergonovine (synonyms ergometrine, ergobasin), which is the specific oxytocic factor of a ergot, is often found in remarkable quantities. In contrast, ergine and hydroxyethylamide of lysergic acid are the main constituents of certain ergot growing on wild grasses, e.g. Paspalum distichum.” 4. Plants of Hallucinogenic Use / The Fungi, p. 37}}</ref>[4] i srodna Periglandula, koje imaju trajnu, simbiotsku vezu s brojnim cvjetničkim lozama, od kojih su najznačajnije Turbina corymbosa i Ipomoea tricolor („jutarnja slava“).[5] Ergolini su koncentrirani u sjemenkama,[6] which have been used for ages by indigenous central/south Americans[7] (tj. sjemenke T. corymbosa poznate su kao ololiuhqui[8][9]) Glavni alkaloidi u sjemenkama izgleda da su ergin i izoergin, ali oni su samo produkti razgradnje hidroksietilamida lizerginske kiseline, izolerginskog hidroksietilamida, hidroksimetiletilamida lizerginske kiseline (sin. ergonovin) i hidroksimetiletilamida izolerginske kiseline (sin. ergonovinin).[10][11][12][13][14][15][16] Svi ostali ergolini kvantificirani su u vrlo malim količinama, osim peniklavina, za koji je utvrđeno da je predominantni ergolin u analizi sjemena I. tricolor iz 2016. godine..[17] Ergolines have been identified in 42 Morning Glory species.[18] Jedini ergolini iz ovih sjemenki koji su ispitani kao izolati su ergin, ergonovin i lizergol, pri čemu lizergol pokazuje najslabiji učinak.[19](refs: Ergine / Psychedelic Effects, Ergometrine / Psychedelic Effects).

Upotreba

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Postoji niz klinički korisnih derivata ergolina u svrhu vazokonstrikcije, liječenja migrena i liječenja Parkinsonove bolesti. Ergolinski alkaloidi pronašli su svoje mjesto u farmakologiji mnogo prije moderne medicine, jer su pripravke ergota babice često koristile u 12. stoljeću za stimulaciju porođaja.[20] Nakon što je Arthur Stoll izolovao ergometrin, terapijska upotreba derivata ergolina postala je dobro istražena.

Indukcija kontrakcija maternice putem pripreme ergota pripisana je ergonovinu, derivatu ergota koji se nalazi u ergotamu, a koji je snažan oksitocinski agens. Na osnovu toga je razjašnjen metergin, sintetski derivat. Iako se koriste za olakšavanje porođaja, derivati ​​ergolina mogu preći u majčino mlijeko i ne smiju se koristiti tokom dojenja. Oni su kontraktori maternice koji mogu povećati rizik od pobačaja tokom trudnoće.[8] Drugi primjer medicinski relevantnih ergolinskih alkaloida je ergotamin, alkaloid koji se također nalazi u ergotaminu. Djeluje kao vazokonstriktor i zabilježeno je da kontrolira migrene. Iz ergotamina, lijekove protiv migrene, dihidroergotamin i metisergid, razvio je Albert Hofmann.[21]

Derivati ​​ergolina, kao što je hidrgin, mješavina dihidroergotoksin mesilata ili ergolin mesilata, također su korišteni u liječenju demencije. Upotreba ovih alkaloida u liječenju Parkinsonove bolesti također je bila istaknuta. Lijekovi poput bromokriptina djeluju kao agonisti dopaminskog receptora, stimulirajući živce koji kontroliraju kretanje.[22] Noviji sintetski derivati ​​ergolina koji su sintetizirani za liječenje Parkinsonove bolesti uključuju pergolid i lisurid, od kojih oba djeluju i kao agonisti dopamina.

Poznati derivat ergolina je psihodelična droga LSD, polusintetski ergolinski alkaloid koga je otkrio Albert Hofmann. LSD se smatra kontroliranom supstancom iz Popisa I. Ergimetrin i ergotamin su uključeni kao prekursori iz Popisa I u Konvenciju Ujedinjenih naroda protiv ilegalne trgovine opojnim drogama i psihotropnim supstancama.[23]

Mehanizam djelovanja

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Mehanizam djelovanja ergolinskih alkaloida varira za svaki derivat. Različite modifikacije mogu se napraviti na ergolinskom skeletu kako bi se dobili medicinski relevantni derivati. Tipovi potencijalnih lijekova na bazi ergolina uključuju dopaminergike, antidopaminergike, serotonergike i antiserotonergike.[24] Ergolinski alkaloidi često ometaju više receptorskih mjesta, što dovodi do negativnih nuspojava i dodatno otežava razvoj lijekova.

Derivati ​​ergolina

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Postoje tri glavne klase derivata ergolina ili supstituiranih ergolina: (1) vodorastvorljivi amidi lizerginske kiseline (tj. lizergamidi); (2) vodonerastvorljivi ergopeptini (tj. ergopeptidi); i (3) klavinska grupa.[25] Samo lizergamidi su poznati po tome što imaju serotonergične psihodelične efekte..[26][27]

NazivR1R2R3
ErginHHH
ErgonovinHCH(CH3)CH2OHH
MeterginHCH(CH2CH3)CH2OHH
MetisergidCH3CH(CH2CH3)CH2OHH
LSDHCH2CH3CH2CH3
  • Ergotoksinska grupa (valin kao aminokiselina vezana za ergolinski dio, na R2 ispod)
    • Ergokristin
    • Ergokornin
      • IUPAC naziv: Ergotaman-3',6',18-trion, 12'-hidroksi-2',5'-bis(1-metiletil)-, (5'-alfa)-
      • CAS registarski broj: 564-36-3
    • alfa-Ergokriptin*** IUPAC ime: Ergotaman-3',6',18-trion, 12'-hidroksi-2'-(1-metiletil)-5'-(2-metilpropil)-, (5'alfa)-
    • beta-Ergokriptin
      • IUPAC naziv: Ergotaman-3',6',18-trion, 12'-hidroksi-2'-(1-metiletil)-5'-(1-metilpropil)-, (5'alfa(S))-
      • CAS broj: 20315-46-2
  • Ergotaminska grupa (alanin na R2)
    • Ertomin
      • IUPAC naziv: Ergotaman-3',6',18-trion, 12'-hidroksi-2'-metil-5'-(fenilmetil)-, (5'-alfa)-
      • CAS broj: 113-15-5
    • Ergovalin
      • IUPAC naziv: Ergotaman-3',6',18-trion, 12'-hidroksi-2'-metil-5'-(1-metiletil)-, (5'alfa)-
      • CAS broj: 2873-38-3
    • alfa-Ergozin
      • IUPAC naziv: Ergotaman-3',6',18-trion, 12'-hidroksi-2'-metil-5'-(2-metilpropil)-, (5'-alfa)-
      • CAS broj: 561-94-4
    • beta-Ergozin
      • IUPAC naziv: Ergotaman-3',6',18-trion, 12'-hidroksi-2'-metil-5'-(1-metilpropil)-, (5'-alfa(S))-
      • CAS broj: 60192-59-8
        Ergopeptidi (strukturna formula)
        Ergopeptidi (strukturna formula)
NazivR1R2R3Aminokiselina na R2Aminokiselina na R3
ErgokristinCH(CH3)2BenzilValinFenilalanin
ErgokorninCH(CH3)2CH(CH3)2ValinValin
alfa-ErgokriptinCH(CH3)2CH2CH(CH3)2ValinLeucin
beta-ErgokriptinCH(CH3)2CH(CH3)CH2CH3 (S)ValinIzoleucin
ErgitaminCH3BenzilAlaninFenilalanin
ErgivalinCH3CH(CH3)2AlaninValin
alfa-ErgozinCH3CH2CH(CH3)2AlaninLeucin
beta-ErgozinCH3CH(CH3)CH2CH3 (S)AlaninIzoleucin
Bromokriptin (polusintetski)BrCH(CH3)2CH2CH(CH3)2ValinLeucin

Također pogledajte

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Reference

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  1. ↑ Schardl CL, Panaccione DG, Tudzynski P (2006). "Ergot alkaloids--biology and molecular biology". The Alkaloids. Chemistry and Biology. Elsevier. 63: 45–86. doi:10.1016/s1099-4831(06)63002-2. ISBN 978-0-12-469563-4. PMID 17133714. Referenca sadrži prazan nepoznati parametar: |1= (pomoć)
  2. ↑ Schiff PL (oktobar 2006). "Ergot and its alkaloids". American Journal of Pharmaceutical Education. 70 (5): 98. doi:10.5688/aj700598 (neaktivno 28. 1. 2025). PMC 1637017. PMID 17149427.CS1 održavanje: DOI nije aktivan od 2025 (link)
  3. ↑ Schultes R (1973). "4. Plants of Hallucinogenic Use / The Fungi". The Botany and Chemistry of Hallucinogens (jezik: engleski). Springfield, IL: Charles Thomas. str. 37. ISBN 9780398064167.
  4. ↑ Wasson RG, Hofmann A, Ruck CA, Webster P (25. 11. 2008) [1978]. Forte R (ured.). The Road to Eleusis: Unveiling the Secret of the Mysteries (jezik: engleski) (30th Anniversary izd.). Berkeley, Calif.: North Atlantic Books. ISBN 978-1-55643-752-6.
    “We analyzed ergot of wheat and ergot of barley in our laboratory and they were found to contain basically the same alkaloids as ergot of rye, viz. alkaloids of the ergotamine and ergotoxine group, ergonovine, and sometimes also traces of lysergic acid amide. As I said before, ergonovine and lysergic acid amide, both psychoactive, are soluble in water whereas the other alkaloids are not.” Albert Hofmann, 2. A Challenging Question and my Answer, p. 42
  5. ↑ Leistner E, Steiner U (3. 2. 2018). "The Genus Periglandula and Its Symbiotum with Morning Glory Plants (Convolvulaceae)". u Anke T, Schüffler A (ured.). Physiology and Genetics (jezik: engleski). Cham: Springer International Publishing. str. 131–147. doi:10.1007/978-3-319-71740-1_5. ISBN 978-3-319-71739-5. Pristupljeno 21. 11. 2024.
  6. ↑ Nowak J, Woźniakiewicz M, Klepacki P, Sowa A, Kościelniak P (maj 2016). "Identification and determination of ergot alkaloids in Morning Glory cultivars". Analytical and Bioanalytical Chemistry. 408 (12): 3093–3102. doi:10.1007/s00216-016-9322-5. PMC 4830885. PMID 26873205.
    “ergine and ergometrine concentration is 12-fold lower in plant samples than in seeds.” Analysis of IP-HB2 young plants
  7. ↑ Ruck CA (2006). Sacred Mushrooms of the Goddess: The Secrets of Eleusis. Berkeley, California: Ronin Publishing, Inc. ISBN 978-1-57951-030-5.
    “Ololiuhqui was far more prominent as an entheogen here in Mesoamerica than those mushrooms; the mushrooms are mentioned only here and there by a few competent chroniclers; yet almost an entire book was devoted to denouncing mainly the ololiuhqui idolatry. The annals of the Inquisition contain many times more autos de fe for ololiuhqui than for mushrooms.” Jonathan Ott, quoted in 15. Mixing the Kykeon Anew (section: Ergine)
  8. 1 2 Schardl CL, Panaccione DG, Tudzynski P (2006). Ergot alkaloids – biology and molecular biology. The Alkaloids. Chemistry and Biology. The Alkaloids: Chemistry and Biology. 63. str. 45–86. doi:10.1016/S1099-4831(06)63002-2. ISBN 978-0-12-469563-4. PMID 17133714.
  9. ↑ Carod-Artal FJ (2015). "Hallucinogenic drugs in pre-Columbian Mesoamerican cultures". Neurologia. 30 (1): 42–49. doi:10.1016/j.nrl.2011.07.003. PMID 21893367.
  10. ↑ Shulgin A (2. 12. 2012) [1976]. "4. Psychotomimetic Agents". u Maxwell G (ured.). Psychopharmacological agents. Medicinal Chemistry. 4. New York: Academic Press. str. 71–72. ISBN 978-0-12-290559-9.
    “These compounds, although well documented as components in the Convolvulaceae, are possibly lost in several of the analyses of alkaloid composition. They are extremely unstable, and are very readily degraded into acetaldehyde and the corresponding amide, ergine or isoergine.” (p. 72)
  11. ↑ Schultes RE, Hofmann A (1973). The Botany and Chemistry of Hallucinogens. Springfield, IL: Charles Thomas. str. 246. ISBN 9780398064167.
    “Later, it was found that ergine and isoergine were present in the seeds to some extent in the form of lysergic acid N-(1-hydroxyethyl) amide and isolysergic acid N-(1-hydroxyethyl) amide, respectively, and that, during the isolation procedure, they easily hydrolize to ergine and isoergine, respectively, and acetaldehyde.” 4. Plants of Hallucinogenic Use / Convolvulaceae, p. 246
  12. ↑ Flieger M, Sedmera P, Vokoun J, R̆ic̄icovā A, R̆ehác̆ek Z (19. 2. 1982). "Separation of four isomers of lysergic acid α-hydroxyethylamide by liquid chromatography and their spectroscopic identification". Journal of Chromatography A. 236 (2): 441–452. doi:10.1016/S0021-9673(00)84895-5. ISSN 0021-9673.
  13. ↑ Ramstad E (1968). "Chemistry of alkaloid formation in ergot". Lloydia. 31: 327–341.
  14. ↑ Kleinerová E, Kybal J (1973). "Ergot alkaloids. IV. Contribution to the biosynthesis of lysergic acid amides". Folia Microbiologica (objavljeno septembar 1973). 18 (5): 390–392. doi:10.1007/BF02875934. PMID 4757982.
  15. ↑ Panaccione DG, Tapper BA, Lane GA, Davies E, Fraser K (oktobar 2003). "Biochemical outcome of blocking the ergot alkaloid pathway of a grass endophyte". Journal of Agricultural and Food Chemistry. 51 (22): 6429–6437. Bibcode:2003JAFC...51.6429P. doi:10.1021/jf0346859. PMID 14558758.
  16. ↑ Panaccione DG (2010). "Ergot alkaloids". u Hofrichter M (ured.). The Mycota, Industrial Applications. 10 (2nd izd.). Berlin-Heidelberg, Germany: Springer-Verlag. str. 195–214.
  17. ↑ Nowak J, Woźniakiewicz M, Klepacki P, Sowa A, Kościelniak P (maj 2016). "Identification and determination of ergot alkaloids in Morning Glory cultivars". Analytical and Bioanalytical Chemistry (objavljeno 14. 2. 2016). 408 (12): 3093–3102. doi:10.1007/s00216-016-9322-5. PMC 4830885. PMID 26873205.
    See Table 3 under “Analysis of different Ipomoea seeds”.
    Concentration values for “LSH”, “Lyzergol/isobars”, penniclavine, and chanoclavine can be obtained by dividing the concentration values of ergine or ergometrine by their relative abundance values and multiplying that number by the relative abundance value of the specified chemical.
  18. ↑ Eich E (12. 1. 2008). "4.2 Ergolines". Solanaceae and convolvulaceae - secondary metabolites: biosynthesis, chemotaxonomy, biological and economic significance: a handbook (jezik: engleski). Berlin, Heidelberg: Springer-Verlag. doi:10.1007/978-3-540-74541-9. ISBN 978-3-540-74540-2. OCLC 195613136.
    Table 4.1 Unambiguously ergoline-positive Ipomoea species (pages 225-227)
    Table 4.4 Unambiguously ergoline-positive Argyreia species (p. 236)
    Table 4.5 Unambiguously ergoline-positive Stictocardia and Turbina species (p. 238)
  19. ↑ Heim E, Heimann H, Lukács G (1968). "Die psychische Wirkung der mexikanischen Droge "Ololiuqui" am Menschen". Psychopharmacologia (jezik: njemački). 13 (1): 35–48. doi:10.1007/BF00401617. PMID 5675457
    c) ᴅ-Lysergol

    “ Promjene su se javile samo pri dozi od 8 mg, sa primjetnim usporavanjem ekspresije i ponašanja. Izraz lica je djelovao bezizražajno, a govor je pokazao smanjenje pet ekspresivnih kvaliteta. Subjektivno je uočeno manje vegetativnih senzacija, ali je postojala izražena inhibicija inicijative.” 3. Rezultati, str. 40
    Prevedeno s njemačkog pomoću ChatGPT.    CS1 održavanje: postscript (link)
  20. ↑ European Commission. Joint Research Centre. Report on the 2017 proficiency test of the European Union reference laboratory for mycotoxins determination of ergot alkaloids in rye. OCLC 1060942360.
  21. ↑ Winkelman M, Roberts TB (2007). Psychedelic medicine : new evidence for hallucinogenic substances as treatments. Praeger Publishers. ISBN 978-0-275-99023-7. OCLC 85813998.
  22. ↑ Lataste X (februar 1984). "The history and pharmacology of dopamine agonists". The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques. 11 (1 Suppl): 118–123. doi:10.1017/S0317167100046266. PMID 6713309.
  23. ↑ "List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control" (PDF). International Narcotics Control Board (Eleventh izd.). Vienna, Austria. januar 2007. Arhivirano s originala (PDF), 27. 2. 2008..
  24. ↑ Mantegani S, Brambilla E, Varasi M (maj 1999). "Ergoline derivatives: receptor affinity and selectivity". Farmaco. 54 (5): 288–296. doi:10.1016/s0014-827x(99)00028-2. PMID 10418123.
  25. ↑ Schardl CL, Panaccione DG, Tudzynski P (2006). Ergot alkaloids – biology and molecular biology. The Alkaloids. Chemistry and Biology. The Alkaloids: Chemistry and Biology. 63. str. 45–86. doi:10.1016/S1099-4831(06)63002-2. ISBN 978-0-12-469563-4. PMID 17133714.
  26. ↑ Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. 36. str. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. 3.1 Amide Modifications of Lysergic Acid Derivatives The simplest ergoline with human psychoactive properties is lysergic acid amide (23, ergine), reported by Hofmann and Tscherter to be the active component in Rivea corymbosa seeds used by the Aztecs in various magical potions and ointments (Hofmann 1971). [...]
  27. ↑ Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi:10.1002/wmts.42. ISSN 2190-460X. Studies of the Amide Portion of Lysergic Acid Derivatives The simplest ergoline with human psychoactive properties, and presumably 5-HT2A agonist activity, is lysergic acid amide (15, ergine), which was reported by Hofmann and Tscherter36 to be the active component in Rivea corymbosa seeds, used by the Aztecs in various magical potions and ointments (Figure 12). [...]

Vanjski linkovi

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Šablon:Ergolini Šablon:Psihodelici Šablon:Hemijske klase psihoaktivnih droga

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