Nicergoline – a drug with the past and the future Review article
Article Sidebar
Published:
Sep 30, 2015
Keywords:
nicergoline, dementia, cerebral circulation, neuroprotection, NGF
Main Article Content
Abstract
Nicergoline, a semi-synthetic analogue of ergot alkaloids, introduced as a vasodilator antagonist of the alpha-1 adrenergic receptor, was synthesized and described in 1970 year in Italy, and is now registered in over 50 countries of the world and used as one of the most popular drugs for disorders of cerebral circulation and related dementias and cognitive defects. Nicergoline also acts on other neurotransmitter receptors, and besides its protective effect on the circulatory system it is a mild stimulant and neuroprotective agent, which is related to its inhibitory effect on oxygen demand and the release of nerve growth factor (NGF). Numerous indications for use vary between countries; they include migraines, platelet aggregation disturbances, and hypertension. It is also used in the treatment of dementia, ophthalmologic disorders (retinal thrombosis, corneal damage, diabetic retinopathy and macular degeneration), in otolaryngology (hearing loss) and vestibular damage (vertigo). Nicergoline is one of the few drugs stimulating the formation of neurotrophins, particularly NGF, making it a potential treatment for an ever increasing number of longevity-related neurodegenerative diseases. Although for some time suspected of dangerous side effects, such as fibrosis and ergotism, in the light of results of recent meta-analysis it may be considered a safe drug.
Article Details
How to Cite
Vetulani, J. (2015). Nicergoline – a drug with the past and the future. Medycyna Faktow (J EBM), 8(3(28), 33-41. Retrieved from https://journalsmededu.pl/index.php/jebm/article/view/2294
Issue
Section
Articles
Copyright © by Medical Education. All rights reserved.
References
1. Vetulani J.: Nicergolina – stary lek z nowymi perspektywami. Neuropsychiatria. Przegl. Klin. 2012; 4: 19-28.
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.
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.
58. McArthur R.A., Carfagna N., Banfi L. et al.: Effects of nicergoline on age-related decrements in radial maze performance and acetylcholine levels. Brain Res. Bull. 1997; 43: 305-311.
59. Landsberg G.: Therapeutic agents for the treatment of cognitive dysfunction syndrome in senior dogs. Prog. Neuropsychopharmacol. Biol. Psychiatry 2005; 29: 471-479.
60. Saletu B., Anderer P., Grunberger J.: Topographic brain mapping of EEG after acute application of ergotalkaloids in the elderly. Arch. Gerontol. Geriatr. 1990; 11: 1-20.
61. Canonico P.L., Sortino M.A., Carfagna N. et al.: Pharmacological basis for the clinical effects of nicergoline in dementia. Geriatria 1996; 5(supl. VIII): 24-48.
62. Iwata E., Miyazaki I., Asanuma M. et al.: Protective effects of nicergoline against hydrogen peroxide toxicity in rat neuronal cell line. Neurosci. Lett. 1998; 251: 49-52.
63. Tanaka M., Yoshida T., Okamoto K. et al.: Antioxidant properties of nicergoline: inhibition of brain autooxidation and superoxide production of neutrophils in rats. Neurosci. Lett. 1998; 284: 68-72.
64. Checler F.: Processing of the beta-amyloid precursor protein and its regulation in Alzheimer’s disease. J. Neurochem. 1995; 65: 1431-1444.
65. Sloane P.D.: Dizziness in primary care: results from the National Ambulatory Medical care Survey. J. Fam. Pract. 1989; 29: 33-38.
66. Hoffman R.M., Einstadter D., Kroenke K.: Evaluating dizziness. Am. J. Med. 1999; 107: 468-478.
67. Colledge N.R., Barr-Hamilton R.M., Lewis S.J. et al.: Evaluation of investigations to diagnose the cause of dizziness in elderly people: a community based controlled study. BMJ 1996; 313: 788-792.
68. Aggarwal N.T., Bennett D.A., Bienias J.L. et al.: The prevalence of dizziness and its association with functional disability in biracial community population. J. Gerontol. A Biol. Sci. Med. Sci. 2000; 55: M288-M292.
69. Felisati G., Pignataro O., Di Girolamo A. et al.: Nicergoline in the treatment of dizziness in elderly patients. A review. Arch. Gerontol. Geriatr. Supl. 2004; 163-170.
70. Teramoto S.: Novel preventive and therapuetic strategy for post-stroke pneumonia. Expert Rev. Neurother. 2009; 9: 1187-200.
71. Ramsey D., Smithard D., Kalra L.: Silent aspiration: what do we know? Dysphagia 2005; 20: 218-225.
72. Arai T., Yoshimi N., Fujiwara H. et al.: Serum substance P concentrations and silent aspiration in elderly patients with stroke. Neurology 2003; 61: 1625-1626.
73. Nishiyama Y., Abea A., Ueda M. et al.: Nicergoline increases serum substance P levels in patients with an ischaemic stroke. Cerebrovasc. Dis. 2010; 29: 194-198.
74. Nakashima T., Hattori N., Okimoto M. et al.: Nicergoline improves dysphagia by upregulating substance P in the elderly. Medicine (Baltimore) 2011; 90: 279-283.
75. Protti R., Cipullo D., Boles Carenini A. et al.: Evaluation of the efficacy of nicergoline on blood flow and ocular function in patients affected by chronic simple glaucoma. Acta Ophthalmol. Scand. Supl. 1998; (227): 42-45.
76. Parisi V., Colacino G., Milazzo G. et al.: Effects of nicergoline on the retinal and cortical electrophysiological responses in glaucoma patients: a preliminary open study. Pharmacol. Res. 1999; 40: 249-255.
77. Kim S.Y., Choi J.S., Joo C.K.: Effects of nicergoline on corneal epithelial wound healing in rat eyes. Invest. Ophthalmol. Vis Sci. 2009; 50: 621-625.
78. Kim S.Y., Yang J., Lee Y.C.: The effects of nicergoline on corneal nerve regeneration in rat corneas after photorefractive keratectomy. Curr. Eye Res. 2011; 36: 29-33.
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.
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.
58. McArthur R.A., Carfagna N., Banfi L. et al.: Effects of nicergoline on age-related decrements in radial maze performance and acetylcholine levels. Brain Res. Bull. 1997; 43: 305-311.
59. Landsberg G.: Therapeutic agents for the treatment of cognitive dysfunction syndrome in senior dogs. Prog. Neuropsychopharmacol. Biol. Psychiatry 2005; 29: 471-479.
60. Saletu B., Anderer P., Grunberger J.: Topographic brain mapping of EEG after acute application of ergotalkaloids in the elderly. Arch. Gerontol. Geriatr. 1990; 11: 1-20.
61. Canonico P.L., Sortino M.A., Carfagna N. et al.: Pharmacological basis for the clinical effects of nicergoline in dementia. Geriatria 1996; 5(supl. VIII): 24-48.
62. Iwata E., Miyazaki I., Asanuma M. et al.: Protective effects of nicergoline against hydrogen peroxide toxicity in rat neuronal cell line. Neurosci. Lett. 1998; 251: 49-52.
63. Tanaka M., Yoshida T., Okamoto K. et al.: Antioxidant properties of nicergoline: inhibition of brain autooxidation and superoxide production of neutrophils in rats. Neurosci. Lett. 1998; 284: 68-72.
64. Checler F.: Processing of the beta-amyloid precursor protein and its regulation in Alzheimer’s disease. J. Neurochem. 1995; 65: 1431-1444.
65. Sloane P.D.: Dizziness in primary care: results from the National Ambulatory Medical care Survey. J. Fam. Pract. 1989; 29: 33-38.
66. Hoffman R.M., Einstadter D., Kroenke K.: Evaluating dizziness. Am. J. Med. 1999; 107: 468-478.
67. Colledge N.R., Barr-Hamilton R.M., Lewis S.J. et al.: Evaluation of investigations to diagnose the cause of dizziness in elderly people: a community based controlled study. BMJ 1996; 313: 788-792.
68. Aggarwal N.T., Bennett D.A., Bienias J.L. et al.: The prevalence of dizziness and its association with functional disability in biracial community population. J. Gerontol. A Biol. Sci. Med. Sci. 2000; 55: M288-M292.
69. Felisati G., Pignataro O., Di Girolamo A. et al.: Nicergoline in the treatment of dizziness in elderly patients. A review. Arch. Gerontol. Geriatr. Supl. 2004; 163-170.
70. Teramoto S.: Novel preventive and therapuetic strategy for post-stroke pneumonia. Expert Rev. Neurother. 2009; 9: 1187-200.
71. Ramsey D., Smithard D., Kalra L.: Silent aspiration: what do we know? Dysphagia 2005; 20: 218-225.
72. Arai T., Yoshimi N., Fujiwara H. et al.: Serum substance P concentrations and silent aspiration in elderly patients with stroke. Neurology 2003; 61: 1625-1626.
73. Nishiyama Y., Abea A., Ueda M. et al.: Nicergoline increases serum substance P levels in patients with an ischaemic stroke. Cerebrovasc. Dis. 2010; 29: 194-198.
74. Nakashima T., Hattori N., Okimoto M. et al.: Nicergoline improves dysphagia by upregulating substance P in the elderly. Medicine (Baltimore) 2011; 90: 279-283.
75. Protti R., Cipullo D., Boles Carenini A. et al.: Evaluation of the efficacy of nicergoline on blood flow and ocular function in patients affected by chronic simple glaucoma. Acta Ophthalmol. Scand. Supl. 1998; (227): 42-45.
76. Parisi V., Colacino G., Milazzo G. et al.: Effects of nicergoline on the retinal and cortical electrophysiological responses in glaucoma patients: a preliminary open study. Pharmacol. Res. 1999; 40: 249-255.
77. Kim S.Y., Choi J.S., Joo C.K.: Effects of nicergoline on corneal epithelial wound healing in rat eyes. Invest. Ophthalmol. Vis Sci. 2009; 50: 621-625.
78. Kim S.Y., Yang J., Lee Y.C.: The effects of nicergoline on corneal nerve regeneration in rat corneas after photorefractive keratectomy. Curr. Eye Res. 2011; 36: 29-33.