Nicergolina – lek z przeszłością i przyszłością Artykuł przeglądowy
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Opublikowane:
wrz 30, 2015
Słowa kluczowe:
nicergolina, otępienie, krążenie mózgowe, neuroprotekcja, NGF
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Abstrakt
Nicergolina, półsyntetyczny analog alkaloidów sporyszu, wprowadzona jako rozszerzający naczynia krwionośne antagonista receptora α1-adrenergicznego, została zsyntetyzowana i opisana w latach 70. ubiegłego wieku we Włoszech. Obecnie jest zarejestrowana w ponad 50 krajach świata i stosowana jako jeden z najpopularniejszych leków w zaburzeniach krążenia mózgowego i związanych z nimi ubytkach poznawczych i otępieniach. Nicergolina wpływa również na inne receptory neuroprzekaźników i poza działaniem ochronnym jest łagodnym środkiem pobudzającym i neuroprotekcyjnym, co łączy się z jej działaniem hamującym zapotrzebowanie na tlen oraz z uwalnianiem czynnika wzrostu nerwów (NGF, nerve growth factor). W różnych krajach zarejestrowana została jako lek w rozmaitych schorzeniach, takich jak: migrena, zaburzenia agregacji płytek krwi czy nadciśnienie tętnicze. Stosuje się ją również w leczeniu otępień, w zaburzeniach okulistycznych (zakrzepica siatkówki, uszkodzenia rogówki, retinopatia cukrzycowa i zwyrodnienie plamki żółtej), laryngologii (niedosłuch) i uszkodzeniach błędnika (zawroty głowy). Nicergolina to jeden z niewielu leków pobudzających tworzenie się neurotrofin, zwłaszcza NGF, co czyni z niej potencjalny lek w wielu schorzeniach neurodegeneracyjnych, których liczba zwiększa się wraz ze wzrostem długowieczności. Chociaż przez pewien czas pojawiały się tezy o jej niebezpiecznych działaniach ubocznych, takich jak powodowanie zwłóknień i wywoływanie ergotyzmu, metaanalizy dowiodły wysokiego poziomu bezpieczeństwa leku.
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Vetulani, J. (2015). Nicergolina – lek z przeszłością i przyszłością . Medycyna Faktów , 8(3(28), 33-41. Pobrano z https://journalsmededu.pl/index.php/jebm/article/view/2294
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Bibliografia
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3. Mason R.: Ergot-derived smart drugs [online: www.smartnutrition.info/Hydergine-Bromocriptine.htm].
4. Pfitzenmeyer P., Foucher P., Dennewald G. et al.: Pleuropulmonary changes induced by ergoline drugs. Eur. Respir. J. 1996; 9: 1013-1019.
5. EMA. Assessment report. 27 September 2013. EMA/750632/2013 [online].
6. Fioravanti M., Nakashima T., Xu J. et al.: A systematic review and meta-analysis assessing adverse event profile and tolerability of nicergoline. BMJ Open 2014; 4(7): e005090.
7. Saletu B., Garg A., Shoeb A.: Safety of nicergoline as an agent for management of cognitive function disorders. Biomed. Res. Int. 2014; 2014: 610103.
8. Bernardi L.: Von der Mutterkorn-Alkaloiden zum Nicergolin Chemische Gesichtspunkte. Arzneimittelforschung 1979; 29: 1204-1206.
9. Guardamagna C., Negri S.: Efficacia clinica della nicergolina nelle vasculopatie cerebrali. Rilievi statistici. Minerva Cardioangiol. 1972; 20: 636-641.
10. Fioravanti M., Flicker L.: Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment. Cochrane Database Syst. Rev. 2001; (4): CD003159.
11. Maestracci P., Grimaud D., Livrelli N. et al.: Correction des effets alphamimetiques du metaraminol par la nicergoline. Ann. Anesthesiol. Fr. 1976; 17: 1255-1259.
12. Forette F., Varin D., Henry J.F. et al.: Traitement de l’hypertension arterielle du sujet age par un alpha-bloquant: la nicergoline. Nouv. Presse Med. 1980; 9: 3685-3688.
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14. Moretti A., Carfagna N., Caccja C. et al.: Effect of ergolines on neurotransmitter systems in the rat brain. Arch. Int. Pharmacodyn. 1988; 294: 33-45.
15. Moretti A., Carfagna N., Caccia C.: Neurochemical effects of ergoline derivatives. W: Heidrich H. (red.): Proof of therapeutical effectiveness of nootropic and vasoactive drug. Berlin: Springer-Verlag 1986: 103-110.
16. Carfagna N., Rossi A.: Nicergoline: biochemical studies on neuronal metabolism. Funct. Neurol. 1989; 4: 177-185.
17. Mirzoyan R.S., Ganshina T.S., Pukhalskaya T.G. et al.: Effects of nicergoline in experimental models related to pathogenesis of migraine. Methods Find. Exp. Clin. Pharmacol. 1989; 11: 671-676.
18. Sims N.R., Bowen D.M., Allen S.J. et al.: Presynaptic cholinergic dysfunction in patients with dementia. J. Neurochem. 1983; 40: 503-509.
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24. Caputi A., Di Luca M., Pastorino L. et al.: Nicergoline and its metabolite induce translocation of PKC isoforms in selective rat brain areas. Neurosci. Res. Commun. 1998; 23: 159-167.
25. Cedazo-Minguez A., Bonecchi L., Winblad B. et al.: Nicergoline stimulates protein kinase C-mediated alpha-secretase processing of the amyloid precursor protein in cultured human neuroblastoma SH-SY5Y cells. Neurochem. Int. 1999; 35(4): 307-315.
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29. Snyder S.H.: Janus faces of nitric oxide, Nature 1993; 364: 577.
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32. Boniece I.R., Wagner J.A.: Growth factors protect PC12 cells against ischemia by a mechanism that is independent of PKA, PKC, and protein synthesis. J. Neurosci. 1993; 13: 4220-4228.
33. Alvarez-Guerra M., Bertholom N., Garay R.P.: Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha 1A-adrenoceptor subtype in the rat. Fundam. Clin. Pharmacol. 1999; 13: 50-58.
34. Robert A., Tran N.N., Giummelly P. et al.: Sensitivity of norepinephrine-evoked vasoconstriction to pertussis toxin in the old rat. Am. J. Physiol. 1998; 274(6 Pt 2): R1604-1612.
35. Baskys A., Hou A.C.: Vascular dementia: pharmacological treatment approaches and perspectives. Clin. Interv. Aging. 2007; 2: 327-335.
36. Cohen S., Levi-Montalcini R., Hamburger V.: A nerve growth-stimulating factor isolated from sarcoma AS 37 and 180. Proc. Natl. Acad. Sci. USA 1954; 40: 1014-1018.
37. Calissano P., Amadoro G., Matrone C. et al.: Does the term ‘trophic’ actually mean anti-amyloidogenic? The case of NGF. Cell Death Differ. 2010; 17: 1126-1133.
38. Cuello A.C., Maysinger D., Garofalo L.: Trophic factor effects on cholinergic innervation in the cerebral cortex of the adult rat brain. Mol. Neurobiol. 1992; 6: 451-461.
39. Barbacid M.: The Trk family of neurotrophin receptors. J. Neurobiol. 1994; 25: 1386-1403.
40. Schliebs R., Rossner S., Bigl V.: Immunolesion by 192IgG-saporin of rat basal forebrain cholinergic system: a useful tool to produce cortical cholinergic dysfunction. Prog. Brain Res. 1996; 109: 253-264.
41. Peterson D.A., Dickinson-Anson H.A., Leppert J.T. et al.: Central neuronal loss and behavioral impairment in mice lacking neurotrophin receptor p75. J. Comp. Neurol. 1999; 404: 1-20.
42. Giardino L., Giuliani A., Battaglia A. et al.: Neuroprotection and aging of the cholinergic system: a role for the ergoline derivative nicergoline (Sermion®). Neuroscience 2002; 109: 487-497.
43. Rylett R.J., Goddard S., Schmidt B.M. et al.: Acetylcholine synthesis and release following continuous intracerebral administration of NGF in adult and aged Fischer-344 rats. J. Neurosci. 1993; 13: 3956-3963.
44. Nishio T., Sunohara N., Furukawa S. et al.: Repeated injection of nicergoline increase the nerve growth factor level in the aged rat brain. Jpn. J. Pharmacol. 1998; 76: 321-323.
45. Lapchak P.A., Hefti F.: Effect of recombinant human nerve growth factor on presynaptic cholinergic function in rat hippocampal slices following partial septohippocampal lesions: measures of 3H-acetylcholine synthesis, 3H-acetylcholine release and choline acetyltransferase activity. Neuroscience 1991; 42: 639-649.
46. Lapchak P.A.: Nerve growth factor pharmacology: application to the treatment of cholinergic neurodegeneration in Alzheimer’s disease. Exp. Neurol. 1993; 124: 16-20.
47. Merighi A., Carmignoto G., Gobbo S. et al.: Neurotrophins in spinal cord nociceptive pathways. Prog. Brain Res. 2004; 146: 291-321.
48. Eriksdotter Jönhagen M., Nordberg A., Amberla K. et al.: Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 1998; 9: 246-257.
49. Walker P., Weichsel M.E. Jr, Fisher D.A. et al.: Thyroxine increases nerve growth factor concentration in adult mouse brain. Science 1979; 204: 427-429.
50. Tirassa P., Stenfors C., Lundeberg T. et al.: Cholecystokinin-8 regulation of NGF concentrations in adult mouse brain through a mechanism involving CCK(A) and CCK(B) receptors. Br. J. Pharmacol. 1998; 123: 1230-1236.
51. Yamada K., Nitta A., Hasegawa T. et al.: Orally active NGF synthesis stimulators: potential therapeutic agents in Alzheimer’s disease. Behav. Brain Res. 1997; 83: 117-122.
52. Hayes V.Y., Isackson P.J., Fabrazzo M. et al.: Induction of nerve growth factor and basic fibroblast growth factor mRNA following clenbuterol: contrasting anatomical and cellular localization. Exp. Neurol. 1995; 132: 33-41.
53. Saletu B., Paulus E., Linzmayer L. et al.: Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: a double-blind, placebocontrolled, clinical and EEG/ERP mapping study. Psychopharmacology 1995; 117: 385-395.
54. Herrmann W.M., Stephan K., Gaede K.: A multicenter randomized double-blind study on the efficacy and safety of nicergoline in patients with multi-infarct dementia. Dement. Geriatr. Cogn. Disord. 1997; 8: 9-17.
55. Schindler U., Rush D.K., Fielding S.: Nootropic drugs: animal models for studying effects on cognition. Drug Dev. Res. 1984; 4: 567-576.
56. Voronina T.A., Nerobkova L.N., Garibova T.L. et al.: Effect of nicergoline on learning andmemory. Methods Find Exp. Clin. Pharmacol. 1988; 10: 431-435.
57. Le Poncin-Lafitte M., Grosdemouge C., Duterte D. et al.: Simultaneous study of haemodynamic, metabolic and behavioural sequelae in a model of cerebral ischaemia in aged rats: effects of nicergoline. Gerontology 1984; 30: 109-119.
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2. Winblad B., Fioravanti M., Dolezal T. et al.: Therapeutic use of nicergoline. Clin. Drug Investig. 2008; 28: 533-552.
3. Mason R.: Ergot-derived smart drugs [online: www.smartnutrition.info/Hydergine-Bromocriptine.htm].
4. Pfitzenmeyer P., Foucher P., Dennewald G. et al.: Pleuropulmonary changes induced by ergoline drugs. Eur. Respir. J. 1996; 9: 1013-1019.
5. EMA. Assessment report. 27 September 2013. EMA/750632/2013 [online].
6. Fioravanti M., Nakashima T., Xu J. et al.: A systematic review and meta-analysis assessing adverse event profile and tolerability of nicergoline. BMJ Open 2014; 4(7): e005090.
7. Saletu B., Garg A., Shoeb A.: Safety of nicergoline as an agent for management of cognitive function disorders. Biomed. Res. Int. 2014; 2014: 610103.
8. Bernardi L.: Von der Mutterkorn-Alkaloiden zum Nicergolin Chemische Gesichtspunkte. Arzneimittelforschung 1979; 29: 1204-1206.
9. Guardamagna C., Negri S.: Efficacia clinica della nicergolina nelle vasculopatie cerebrali. Rilievi statistici. Minerva Cardioangiol. 1972; 20: 636-641.
10. Fioravanti M., Flicker L.: Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment. Cochrane Database Syst. Rev. 2001; (4): CD003159.
11. Maestracci P., Grimaud D., Livrelli N. et al.: Correction des effets alphamimetiques du metaraminol par la nicergoline. Ann. Anesthesiol. Fr. 1976; 17: 1255-1259.
12. Forette F., Varin D., Henry J.F. et al.: Traitement de l’hypertension arterielle du sujet age par un alpha-bloquant: la nicergoline. Nouv. Presse Med. 1980; 9: 3685-3688.
13. Carpéné C., Lafontan M., Berlan M.: Mise en evidence d’une potentialite alpha 2-bloquante de la nicergoline par utilisation du recepteur alpha-adrenergique du tissu adipeux. J. Pharmacol. 1983; 14: 57-66.
14. Moretti A., Carfagna N., Caccja C. et al.: Effect of ergolines on neurotransmitter systems in the rat brain. Arch. Int. Pharmacodyn. 1988; 294: 33-45.
15. Moretti A., Carfagna N., Caccia C.: Neurochemical effects of ergoline derivatives. W: Heidrich H. (red.): Proof of therapeutical effectiveness of nootropic and vasoactive drug. Berlin: Springer-Verlag 1986: 103-110.
16. Carfagna N., Rossi A.: Nicergoline: biochemical studies on neuronal metabolism. Funct. Neurol. 1989; 4: 177-185.
17. Mirzoyan R.S., Ganshina T.S., Pukhalskaya T.G. et al.: Effects of nicergoline in experimental models related to pathogenesis of migraine. Methods Find. Exp. Clin. Pharmacol. 1989; 11: 671-676.
18. Sims N.R., Bowen D.M., Allen S.J. et al.: Presynaptic cholinergic dysfunction in patients with dementia. J. Neurochem. 1983; 40: 503-509.
19. Carfagna N., Di Clemente A., Cavanus S. et al.: Modulation of hippocampal ACh release by chronic nicergoline treatment in freely moving young and aged rats. Neurosci. Lett. 1995; 197: 195-198.
20. Ogawa N., Asanuma M., Hirata H. et al.: Cholinergic deficits in aged rat brain are corrected with nicergoline. Arch. Geront. Geriatr. 1993; 16: 103-110.
21. Stokes C.E., Gillon K.R.W., Hawthrone J.N.: Free and total lipid myo-inositol concentrations decrease with age in human brains. Biochem. Biophys. Acta 1983; 735: 136-138.
22. Stokes C.E., Hawthorne J.N.: Reduced phosphoinositide concentrations in anterior temporal cortex of Alzheimer-disease brains. J. Neurochem. 1987; 48: 1018-1021.
23. Carfagna N., Cavanus S., Damiani D. et al.: Modulation of phosphoinositide turnover by chronic nicergoline in rat brain. Neurosci. Lett. 1996; 209: 189-192.
24. Caputi A., Di Luca M., Pastorino L. et al.: Nicergoline and its metabolite induce translocation of PKC isoforms in selective rat brain areas. Neurosci. Res. Commun. 1998; 23: 159-167.
25. Cedazo-Minguez A., Bonecchi L., Winblad B. et al.: Nicergoline stimulates protein kinase C-mediated alpha-secretase processing of the amyloid precursor protein in cultured human neuroblastoma SH-SY5Y cells. Neurochem. Int. 1999; 35(4): 307-315.
26. Cowburn R.F., Fowler C.J., O’Neill C.: Neurotransmitter receptor/G-protein mediated signal transduction in Alzheimer’s disease brain. Neurodegeneration 1996; 5: 483-488.
27. Sobreviela T., Jaffar S., Mufson E.J.: Tyrosine kinase A, galanin and nitric oxide synthase within basal forebrain neurons in the rat. Neuroscience 1998; 87: 447-461.
28. Giardino L., Zanni M., Pozza M. et al.: Nitric oxide synthase mRNA regulation by nicergoline treatment in the brain of old rats. In: Proceedings of the 4th International Congress of the European Society for Clinical Neuropharmacology. Monduzzi Internazional, Bologna 1997: 45-49.
29. Snyder S.H.: Janus faces of nitric oxide, Nature 1993; 364: 577.
30. Saletu B., Grünberger J., Lintzmayer L. et al.: Brain protection of nicergoline against hypoxia: EEG brain mapping and psychometry. J. Neural. Transm. Park. Dis. Dement. Sect. 1990; 2: 305-325.
31. Sortino M.A., Battaglia A., Pamparana F. et al.: Neuroprotective effects of nicergoline in immortalized neurons. Eur. J. Pharmacol. 1999; 368: 285-290.
32. Boniece I.R., Wagner J.A.: Growth factors protect PC12 cells against ischemia by a mechanism that is independent of PKA, PKC, and protein synthesis. J. Neurosci. 1993; 13: 4220-4228.
33. Alvarez-Guerra M., Bertholom N., Garay R.P.: Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha 1A-adrenoceptor subtype in the rat. Fundam. Clin. Pharmacol. 1999; 13: 50-58.
34. Robert A., Tran N.N., Giummelly P. et al.: Sensitivity of norepinephrine-evoked vasoconstriction to pertussis toxin in the old rat. Am. J. Physiol. 1998; 274(6 Pt 2): R1604-1612.
35. Baskys A., Hou A.C.: Vascular dementia: pharmacological treatment approaches and perspectives. Clin. Interv. Aging. 2007; 2: 327-335.
36. Cohen S., Levi-Montalcini R., Hamburger V.: A nerve growth-stimulating factor isolated from sarcoma AS 37 and 180. Proc. Natl. Acad. Sci. USA 1954; 40: 1014-1018.
37. Calissano P., Amadoro G., Matrone C. et al.: Does the term ‘trophic’ actually mean anti-amyloidogenic? The case of NGF. Cell Death Differ. 2010; 17: 1126-1133.
38. Cuello A.C., Maysinger D., Garofalo L.: Trophic factor effects on cholinergic innervation in the cerebral cortex of the adult rat brain. Mol. Neurobiol. 1992; 6: 451-461.
39. Barbacid M.: The Trk family of neurotrophin receptors. J. Neurobiol. 1994; 25: 1386-1403.
40. Schliebs R., Rossner S., Bigl V.: Immunolesion by 192IgG-saporin of rat basal forebrain cholinergic system: a useful tool to produce cortical cholinergic dysfunction. Prog. Brain Res. 1996; 109: 253-264.
41. Peterson D.A., Dickinson-Anson H.A., Leppert J.T. et al.: Central neuronal loss and behavioral impairment in mice lacking neurotrophin receptor p75. J. Comp. Neurol. 1999; 404: 1-20.
42. Giardino L., Giuliani A., Battaglia A. et al.: Neuroprotection and aging of the cholinergic system: a role for the ergoline derivative nicergoline (Sermion®). Neuroscience 2002; 109: 487-497.
43. Rylett R.J., Goddard S., Schmidt B.M. et al.: Acetylcholine synthesis and release following continuous intracerebral administration of NGF in adult and aged Fischer-344 rats. J. Neurosci. 1993; 13: 3956-3963.
44. Nishio T., Sunohara N., Furukawa S. et al.: Repeated injection of nicergoline increase the nerve growth factor level in the aged rat brain. Jpn. J. Pharmacol. 1998; 76: 321-323.
45. Lapchak P.A., Hefti F.: Effect of recombinant human nerve growth factor on presynaptic cholinergic function in rat hippocampal slices following partial septohippocampal lesions: measures of 3H-acetylcholine synthesis, 3H-acetylcholine release and choline acetyltransferase activity. Neuroscience 1991; 42: 639-649.
46. Lapchak P.A.: Nerve growth factor pharmacology: application to the treatment of cholinergic neurodegeneration in Alzheimer’s disease. Exp. Neurol. 1993; 124: 16-20.
47. Merighi A., Carmignoto G., Gobbo S. et al.: Neurotrophins in spinal cord nociceptive pathways. Prog. Brain Res. 2004; 146: 291-321.
48. Eriksdotter Jönhagen M., Nordberg A., Amberla K. et al.: Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 1998; 9: 246-257.
49. Walker P., Weichsel M.E. Jr, Fisher D.A. et al.: Thyroxine increases nerve growth factor concentration in adult mouse brain. Science 1979; 204: 427-429.
50. Tirassa P., Stenfors C., Lundeberg T. et al.: Cholecystokinin-8 regulation of NGF concentrations in adult mouse brain through a mechanism involving CCK(A) and CCK(B) receptors. Br. J. Pharmacol. 1998; 123: 1230-1236.
51. Yamada K., Nitta A., Hasegawa T. et al.: Orally active NGF synthesis stimulators: potential therapeutic agents in Alzheimer’s disease. Behav. Brain Res. 1997; 83: 117-122.
52. Hayes V.Y., Isackson P.J., Fabrazzo M. et al.: Induction of nerve growth factor and basic fibroblast growth factor mRNA following clenbuterol: contrasting anatomical and cellular localization. Exp. Neurol. 1995; 132: 33-41.
53. Saletu B., Paulus E., Linzmayer L. et al.: Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: a double-blind, placebocontrolled, clinical and EEG/ERP mapping study. Psychopharmacology 1995; 117: 385-395.
54. Herrmann W.M., Stephan K., Gaede K.: A multicenter randomized double-blind study on the efficacy and safety of nicergoline in patients with multi-infarct dementia. Dement. Geriatr. Cogn. Disord. 1997; 8: 9-17.
55. Schindler U., Rush D.K., Fielding S.: Nootropic drugs: animal models for studying effects on cognition. Drug Dev. Res. 1984; 4: 567-576.
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