Википедија

Upotreba organofosfata u terapiji

Upotreba organofosfata u terapiji i pred njihovog dokazanog toksičnog dejstva na organizam ljudi, pokazala se korisna kod određenih patoloških stanja, naravno u drugojačijim dozama i načinima primene, od onih za pesticide.[1]

Takrine je 1990-tih korišćen u lečenju Alchajmerove bolesti

Opšte razmatranja

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Nekoliko organofosfatnih jedinjenja, koji se koriste i kao insekticidi, čije je dejstvo istraživano u humanoj terapiji zasnivalo se pre svaga na dejstvu holinesteraze (koja u velikim dozama čini efikasanim neki pesticid),[2] da može biti koristna u drugim dozama za lečenje demencije u medicini.[3]

Metrifonat, je jedan od preparata iz grupe OFJ koji se koristi za lečenje šistosomijaze, a trenutno prolazi i kroz istraživanje kao lek za lečenje primarne degenerativne demencije.

Organofosfati piridostigmin i fizostigmin koji su karbamatne antiholinesteraze već dugi niz godina korišćene su za lečenje mijastenije gravis.

Iako su kratkodelujuće antiholinesteraze generalno bezbedne, izveštaji o njihovom neželjenom dejstvu su povezani sa sličnom dejstvima nakon zloupotrebe pesticida.[4]

Lek kao što je rivastigmin za sada se široko korisi kod blage do umereno teške Alchajmerove bolesti. Njegova neželjena dejstva su mučnina, povraćanje i gubitak težine zbog povećanja holinergičke aktivnosti.

Sung i saradnici su prijavili sposobnost ovih supstanci da indukuju modulaciju nikotinskog receptora, i obijasnili da dalja istraživanja mogu rezultovati uspešnim delovanje ovih lekova daljim razvojem efikasnijih agenasa.[5]

 
Primeri organofosfata i srodnih jedinjenja su fosfatidilholin, trifenilfosfat, ciklofosfamid, paration i cinkov ditiofosfat.

Istorija upotrebe organofosfata u terapiji

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Fostostigmin je korišćen za lečenje glaukoma (na slici) u 1870-tim godinama.
  • Prvi organofosfat je sintetisan 1850. godine.
  • Fostostigmin je korišćen za lečenje glaukoma u 1870.tim godinama.
  • Do tridesetih godina p20. veka sintetički inhibitori holinesteraze korišćeni su za lečenje skeletnih mišića i autonomnih poremećaje.
  • Neki organofosfati su korišćeni u lečenju parkinsonizma. Godine 1986, Testiranje je počelo 1986. godine sa tacrineom, prvim inhibitor holinesteraze koji korišćen za lečenje Alchajmerove bolest, prvo puštenim u kliničku upotrebu 1993. godine, a potom nekoliko godina kasnije povučenim iz upotrebe. Krvnomoždana barijera bila je ograničavajući faktor za razvoj inhibitora holinesteraze u lečenju demencije — Alchajmerove bolesti.
  • Piridostigmin je testiran na umor postpolio sindroma, ali nije pokazao nikakvu korist.[6]

Izvori

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  1. ^ „Therapeutic uses of organophosphates U:Frances M Dyro Organophosphates”. emedicine.medscape.com. Pristupljeno 14. 5. 2018. 
  2. ^ Y. Solberg and M. Belkin, The role of excitotoxicity in organophosphorous nerve agents central poisoning, Trends in Pharmacological Sciences, 18, 6, (183), (1997).
  3. ^ Lotti M, Becker CE, Aminoff MJ. Organophosphate polyneuropathy: pathogenesis and prevention. Neurology. 1984 May. 34(5):658-62. [Medline].
  4. ^ Aamer Saeed, Muhammad Shakil Shah, Fayaz Ali Larik, Shafi Ullah Khan, Pervaiz Ali Channar, Ulrich Flörke and Jamshed Iqbal, Synthesis, computational studies and biological evaluation of new 1-acetyl-3-aryl thiourea derivatives as potent cholinesterase inhibitors, Medicinal Chemistry Research, 26, 8, (1635), (2017).
  5. ^ Sung JJ, Kim SJ, Lee HB, et al. Anticholinesterase induces nicotinic receptor modulation. Muscle Nerve. 1998 Sep. 21(9):1135-44. [Medline].
  6. ^ Trojan DA, Collet JP, Shapiro S, et al. A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome. Neurology. 1999 Oct 12. 53(6):1225-33. [Medline].

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