Nicergoline

Last updated
Nicergoline
Nicergoline Structure V.1.svg
Clinical data
Trade names Sermion
Other names[(8β)-10-Methoxy-1,6-dimethylergolin-8-yl]methyl 5-bromopyridine-3-carboxylate
AHFS/Drugs.com International 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%
Metabolism Extensive First-pass metabolism
Elimination half-life 13–20 hours
Identifiers
  • [(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 InfoCard 100.044.252 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C24H26BrN3O3
Molar mass 484.394 g·mol−1
3D model (JSmol)
  • Brc1cc(cnc1)C(=O)OC[C@@H]3C[C@]4(OC)c5cccc2c5c(cn2C)C[C@H]4N(C3)C
  • 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 Yes check.svgY
  • Key:YSEXMKHXIOCEJA-FVFQAYNVSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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]

Contents

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:

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. [2]

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. [7] The IC50 of nicergoline in vitro has been reported to be 0.2 nM. [8] 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. [9] [10] 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. [2] The major metabolites of nicergoline, MMDL and MDL, show low or no affinity for adrenergic, serotonin, dopamine, or acetylcholine receptors. [2]

Society and culture

Generic names

Nicergoline is the generic name of the drug and its INN, USAN, BAN, and DCF. [11] [12]

Related Research Articles

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Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken orally or by intravenous injection. The formulation that is taken orally comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.

<span class="mw-page-title-main">Ergoline</span> Chemical compound

Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of these are implicated in the condition ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.

<span class="mw-page-title-main">Ergotamine</span> Chemical compound in the ergot family of alkaloids

Ergotamine, sold under the brand names Cafergot and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor.

<span class="mw-page-title-main">Triptan</span> Class of pharmaceutical drugs

Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, they do not provide preventive treatment and are not considered a cure. They are not effective for the treatment of tension–type headache, except in persons who also experience migraines. Triptans do not relieve other kinds of pain.

<span class="mw-page-title-main">Ergoloid</span> Chemical compound

Ergoloid mesylates (USAN), co-dergocrine mesilate (BAN) or dihydroergotoxine mesylate, trade name Hydergine, is a mixture of the methanesulfonate salts of three dihydrogenated ergot alkaloids.

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Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an ergot alkaloid used to treat migraines. It is a derivative of ergotamine. It is administered as a nasal spray or injection and has an efficacy similar to that of sumatriptan. Nausea is a common side effect.

<span class="mw-page-title-main">Lysergic acid hydroxyethylamide</span> Chemical compound

D-Lysergic acid α-hydroxyethylamide, also known as D-lysergic acid methyl carbinolamide, is a is a Lysergamide and alkaloid of the Ergoline family, it is present in higher concentrations in the parasitic fungi species "Claviceps", mainly the Claviceps Paspali, also in Claviceps Purpurea. This fungi grows in various species in the Convolvulaceae family like the Ipomoea violacea, the Rivea corymbosa (Ololiuhqui), and the Argyreia nervosa. Heavenly Blue Morning Glory and Hawaiian Baby Woodrose especially contain high amounts of LSH, with content varying between species and by how fresh are the seeds. LSH is a psychoactive Ergoline and has effects similar to LSD due to similarity in the structure and is the main psychoactive compound found in Claviceps Paspali and in (fresh) Heavenly Blue Morning Glory Seeds. LSH is unstable and breaks down into LSA quickly, so old seeds often only contains LSA and iso-LSA. When the seeds are fresh, they contain significantly higher amounts of LSH.

<span class="mw-page-title-main">Methylergometrine</span> Chemical compound

Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.

<span class="mw-page-title-main">Methysergide</span> Chemical compound

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<span class="mw-page-title-main">Lisuride</span> Chemical compound

Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

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References

  1. ↑ https://www.ema.europa.eu/documents/psusa/nicergoline-list-nationally-authorised-medicinal-products-psusa/00002150/202005_en.pdf [ bare URL PDF ]
  2. 1 2 3 4 5 Zajdel P, Bednarski M, Sapa J, Nowak G (April 2015). "Ergotamine and nicergoline - facts and myths". Pharmacological Reports. 67 (2): 360–363. doi:10.1016/j.pharep.2014.10.010. PMID   25712664. S2CID   22768662.
  3. ↑ Fioravanti M, Flicker L (2001). "Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment". The Cochrane Database of Systematic Reviews. 2001 (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. 1 2 3 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. ↑ 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". Fundamental & Clinical Pharmacology. 13 (1): 50–58. doi:10.1111/j.1472-8206.1999.tb00320.x. PMID   10027088. S2CID   43871763.
  8. ↑ Moretti A, Carfagna N, Caccia C, Carpentieri M (1988). "Effect of ergolines on neurotransmitter systems in the rat brain". Archives Internationales de Pharmacodynamie et de Therapie. 294: 33–45. PMID   2906797.
  9. ↑ Nishio T, Sunohara N, Furukawa S, Akiguchi I, Kudo Y (March 1998). "Repeated injections of nicergoline increase the nerve growth factor level in the aged rat brain". Japanese Journal of Pharmacology. 76 (3): 321–323. doi: 10.1254/jjp.76.321 . PMID   9593228.
  10. ↑ Mizuno T, Kuno R, Nitta A, Nabeshima T, Zhang G, Kawanokuchi J, et al. (December 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.
  11. ↑ 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.
  12. ↑ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 727–. ISBN   978-3-88763-075-1.
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