Nicergoline

Nicergoline, sold under the brand name Sermion among others, is an ergot derivative used to treat senile dementia and other disorders with vascular origins. Internationally it has been used for frontotemporal dementia as well as early onset in Lewy body dementia and Parkinson's dementia. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells. It has similar vasoactive properties in other areas of the body, particularly the lungs. Unlike many other ergolines, such as ergotamine, nicergoline is not associated with cardiac fibrosis.[2]

Nicergoline
Clinical data
Trade namesSermion
Other names[(8β)-10-Methoxy-1,6-dimethylergolin-8-yl]methyl 5-bromopyridine-3-carboxylate
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • Not recommended
Routes of
administration		By mouth, intramuscular, intravenous
ATC code
Legal status
Legal status
  • EU: Rx-only [1]
Pharmacokinetic data
Bioavailability<5%
Protein binding>90%
MetabolismExtensive First-pass metabolism
Elimination half-life13–20 hours
Identifiers
IUPAC name
  • [(6aR,9R,10aS)-10a-methoxy-4,7-dimethyl-6a,8,9,10-tetrahydro-6H-indolo[4,3-fg]quinolin-9-yl]methyl 5-bromopyridine-3-carboxylate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.044.252
Chemical and physical data
FormulaC24H26BrN3O3
Molar mass484.394 g·mol−1
3D model (JSmol)
SMILES
  • Brc1cc(cnc1)C(=O)OC[C@@H]3C[C@]4(OC)c5cccc2c5c(cn2C)C[C@H]4N(C3)C
InChI
  • InChI=1S/C24H26BrN3O3/c1-27-13-17-8-21-24(30-3,19-5-4-6-20(27)22(17)19)9-15(12-28(21)2)14-31-23(29)16-7-18(25)11-26-10-16/h4-7,10-11,13,15,21H,8-9,12,14H2,1-3H3/t15-,21-,24+/m1/s1 Y
  • Key:YSEXMKHXIOCEJA-FVFQAYNVSA-N Y
 NY (what is this?)  (verify)

It is used for vascular disorders such as cerebral thrombosis and atherosclerosis, arterial blockages in the limbs, Raynaud's disease, vascular migraines, and retinopathy.

Nicergoline has been registered in over fifty countries and has been used for more than three decades for the treatment of cognitive, affective, and behavioral disorders of older people.[3]

Medical uses

Nicergoline is used in the following cases:

  • Acute and chronic cerebral metabolic-vascular disorders (cerebral arteriosclerosis, thrombosis and cerebral embolism, transitory cerebral ischaemia). Acute and chronic peripheral metabolic-vascular disorders (organic and functional arteriopathies of the limbs), Raynaud’s disease and other syndromes caused by altered peripheral irrigation.
  • Migraines of vascular origin
  • Coadjutant therapy in clinical situations accompanied by platelet hyper-aggregability, arterial tension.
  • Corio-retinal vascular disorders: diabetic retinopathy, macular degeneration and retinal angiosclerosis
  • Oto-vestibular problems of a vascular nature: dizziness, auditory hallucinations, hypoacusis.

Dosages for known conditions are usually administered at 5–10 mg three times a day, however anti-aging preventative purposes may want to consider 5 mg once or twice a day more adequate.[4]

Contraindications

Persons suffering from acute bleeding, myocardial infarction (heart conditions), hypertension, bradycardia or using alpha or beta receptor agonists should consult with their physician before use. Although toxicology studies have not shown nicergoline to have any teratogenic effect, the use of this medicine during pregnancy should be limited to those cases where it is absolutely necessary.

On 28 June 2013, the European Medicines Agency recommended restricting the use of medicines containing ergot derivatives, including nicergoline. They stated that "these medicines should no longer be used to treat several conditions involving blood circulation problems or problems with memory and sensation, or to prevent migraine headaches, since the risks are greater than the benefits in these indications. This is based on a review of data showing an increased risk of fibrosis (formation of excess connective tissue that can damage organs and body structures) and ergotism (symptoms of ergot poisoning, such as spasms and obstructed blood circulation) with these medicines.[5] However, only a subset of ergolines are associated with fibrosis and evidence suggests that nicergoline does not carry the same fibrotic risk like other ergoline derivatives such as ergotamine.[2]

Nicergoline is considered unsafe in porphyria.[6]

Side effects

The side effects of nicergoline are usually limited to nausea, hot flushes, mild gastric upset, hypotension and dizziness.[6] At high drug dosages, bradycardia, increased appetite, agitation, diarrhea and perspiration were reported. Most of the available literature suggests that the side effects of nicergoline are mild and transient.[7]

Interactions

Nicergoline is known to enhance the cardiac depressive effects of propranolol.[6] At high dosages, it is advisable to seek one’s physician's guidance if combining with potent vasodilators such as bromocriptine, Ginkgo biloba, picamilon, vinpocetine or xantinol nicotinate.

Pharmacology

Pharmacodynamics

Nicergoline is an ergot alkaloid derivative that acts as a potent and selective α1A-adrenergic receptor antagonist.[8] The IC50 of nicergoline in vitro has been reported to be 0.2 nM.[9] The primary action of nicergoline is to increase arterial blood flow by vasodilation. Furthermore, it is known that nicergoline inhibits platelet aggregation. Studies have shown that nicergoline also increases nerve growth factor in the aged brain.[10][11] In addition to the α1A-adrenergic receptor, nicergoline is an antagonist of the serotonin 5-HT1A receptor (IC50 = 6 nM) and shows moderate affinity for serotonin 5-HT2 and α2-adrenergic receptors and low affinity for the dopamine D1 and D2 and muscarinic acetylcholine M1 and M2 receptors.[12] The major metabolites of nicergoline, MMDL and MDL, show low or no affinity for adrenergic, serotonin, dopamine, or acetylcholine receptors.[12]

Society and culture

Generic names

Nicergoline is the generic name of the drug and its INN, USAN, BAN, and DCF.[13][14]

References
  1. https://www.ema.europa.eu/documents/psusa/nicergoline-list-nationally-authorised-medicinal-products-psusa/00002150/202005_en.pdf
  2. Zajdel, P; Bednarski, M; Sapa, J; Nowak, G (2015). "Ergotamine and nicergoline - facts and myths". Pharmacological Reports. 67 (2): 360–3. doi:10.1016/j.pharep.2014.10.010. PMID 25712664.
  3. Fioravanti M, Flicker L (2001). "Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment". Cochrane Database Syst Rev (4): CD003159. doi:10.1002/14651858.CD003159. PMC 7025776. PMID 11687175.
  4. Nicergoline drug insert, Pharmacia & Upjohn, October 2000
  5. European Medicines Agency (28 June 2013), "New restrictions on use of medicines containing ergot derivatives", Press Release
  6. Sweetman SC, ed. (2009). "Supplementary drugs and other substances". Martindale: It should be considered as last option in temporal impediments and build up of Lewy Bodies and obstructions contributed to "dementia" The complete drug reference (36th ed.). London: Pharmaceutical Press. p. 2352. ISBN 978-0-85369-840-1.
  7. Zajdel P, Bednarski M, Sapa J, Nowak G (2015). "Ergotamine and nicergoline - facts and myths". Pharmacol Rep. 67 (2): 360–363. doi:10.1016/j.pharep.2014.10.010. PMID 25712664.{{cite journal}}: CS1 maint: uses authors parameter (link)
  8. Alvarez-Guerra M, Bertholom N, Garay RP (1999). "Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha 1A-adrenoceptor subtype in the rat". Fundam Clin Pharmacol. 13 (1): 50–8. doi:10.1111/j.1472-8206.1999.tb00320.x. PMID 10027088. S2CID 43871763.
  9. Moretti A, Carfagna N, Caccia C, Carpentieri M (1988). "Effect of ergolines on neurotransmitter systems in the rat brain". Arch Int Pharmacodyn Ther. 294: 33–45. PMID 2906797.
  10. Nishio T, Sunohara N, Furukawa S, Akiguchi I, Kudo Y (1998). "Repeated injections of nicergoline increase the nerve growth factor level in the aged rat brain and production of brain-derived neurotrophic factor by activeted astrocytes". The Japanese Journal of Pharmacology. 76 (3): 321–323. doi:10.1254/jjp.76.321. PMID 9593228.
  11. Mizuno T, Kuno R, Nitta A, Nabeshima T, Zhang G, Kawanokuchi J, Wang J, Jin S, Takeuchi H, Suzumura A (2005). "Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes". Brain Research. 1066 (1–2): 78–85. doi:10.1016/j.brainres.2005.10.050. PMID 16325157. S2CID 34963522.
  12. Zajdel P, Bednarski M, Sapa J, Nowak G (April 2015). "Ergotamine and nicergoline - facts and myths". Pharmacol Rep. 67 (2): 360–3. doi:10.1016/j.pharep.2014.10.010. PMID 25712664.
  13. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 864–. ISBN 978-1-4757-2085-3.
  14. Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 727–. ISBN 978-3-88763-075-1.
  • "Nicergoline". Drug Information Portal. U.S. National Library of Medicine.
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