NICERGOLINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H26BrN3O3
Molecular Weight	484.386
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@]12C[C@@H](COC(=O)C3=CN=CC(Br)=C3)CN(C)[C@@H]1CC4=CN(C)C5=C4C2=CC=C5

InChI

InChIKey=YSEXMKHXIOCEJA-FVFQAYNVSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Ergot_derivatives-containing_products/WC500161305.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68009530

Nicergoline is a semisynthetic ergoline derivative that has been used as a cerebral vasodilator and in peripheral vascular disease. Nicergoline seems to have an action: (i) as an alpha1-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Nicergoline has been suggested to ameliorate cognitive deficits in cerebrovascular disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-1a adrenergic receptor 67 Target ID: CHEMBL319 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Ergot_derivatives-containing_products/WC500161305.pdf	Antagonist 2849		7.26 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Dementia 27 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18666801	Palliative	Approved 8583	SERMION Approved Use Dementia (including Alzheimer's disease and vascular dementia)
Alzheimer’s disease 278 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18666801	Palliative	Approved 8583	SERMION Approved Use Dementia (including Alzheimer's disease and vascular dementia)
Vascular dementia 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18666801	Palliative	Approved 8583	SERMION Approved Use Dementia (including Alzheimer's disease and vascular dementia)

C_max

Value	Dose	Co-administered	Analyte	Population
34.504 ng/mL CLINICAL TRIAL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760819/pdf/main.pdf	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		NICERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
388.38 ng × h/mL CLINICAL TRIAL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760819/pdf/main.pdf	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		NICERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.427 h CLINICAL TRIAL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760819/pdf/main.pdf	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		NICERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/	Disc. AE: Gastric pain, Hot flushes... AEs leading to discontinuation/dose reduction: Gastric pain (grade 2, 0.65%) Hot flushes (grade 2, 0.65%) Hypertensive crisis (0.65%) Confusional state (0.65%) Syncopal attack (0.65%) Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/

AEs

AE	Significance	Dose	Population
Confusional state	0.65% Disc. AE	60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/
Hypertensive crisis	0.65% Disc. AE	60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/
Syncopal attack	0.65% Disc. AE	60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/
Gastric pain	grade 2, 0.65% Disc. AE	60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/
Hot flushes	grade 2, 0.65% Disc. AE	60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2646350/

PubMed

Title	Date	PubMed
[Haemodynamic and metabolic effects of exercise test in diabetic patients with arteritis treated or not with nicergoline (author's transl)].	1981 Sep 18-25	6270809
Systemic and carotid haemodynamics and plasma renin activity during deliberate hypotension in dogs: a comparison of sodium nitroprusside with nicergoline.	1984 Mar	6399253
[Plasma renin activity and prostaglandin E2 in hypotension induced by nicergoline].	1985	3893236
[Nicergoline to reduce intraoperative blood pressure increases in hypertensive patients].	1985 Nov	4092160
[Pharmacological analysis of memory disorders of different origins].	1989 Jun	2571367
[A case of parkinsonism induced by an oral contraceptive].	1992 Feb	1567736
Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment.	2001	11687175
[Current strategies of pathogenetic therapy of Alzheimer's disease].	2001	11523421
[Sermion in the treatment of patients with neurological diseases].	2001 Aug	11569346
Pulmonary function in men after repeated sessions of oxygen breathing at 0.25 MPa for 90 min.	2001 Mar	11277287
Effect of an alpha-blocker (Nicergoline) and of a beta-blocker (Acebutolol) on the in vitro biosynthesis of vascular extracellular matrix.	2001 May	11428166
Acute interstitial nephritis due to nicergoline (Sermion).	2002	12372954
Neuroprotection and aging of the cholinergic system: a role for the ergoline derivative nicergoline (Sermion).	2002	11823061
Inhibition by brimonidine of forskolin-induced nitrite production in isolated pig ciliary processes.	2002 Aug	12147609
Plasticity of GABA(a) system during ageing: focus on vestibular compensation and possible pharmacological intervention.	2002 Mar 1	11852033
[Nicergoline in the treatment of patients after a mild ischemic stroke].	2002 Nov-Dec	12715685
First derivative ratio spectrophotometric, HPTLC-densitometric, and HPLC determination of nicergoline in presence of its hydrolysis-induced degradation product.	2002 Oct 15	12367672
Antioxidant properties of MDL and MMDL, two nicergoline metabolites, during chronic administration of haloperidol.	2002 Oct 18	12393061
[1-13C]Glucose entry in neuronal and astrocytic intermediary metabolism of aged rats. A study of the effects of nicergoline treatment by 13C NMR spectroscopy.	2003 Mar 14	12646315
[Neurotransmitter mechanism of the tropoxin effect in comparison with other antimigraine preparations].	2003 May-Jun	12924226
Nicergoline in the treatment of dizziness in elderly patients. A review.	2004	15207410
Neuroprotection: a realistic goal for aged brain?	2004	14977213
Sudden hearing loss as a first complication of long-standing Type 1 diabetes mellitus: a case report.	2004 Jan	14706062
[Nicergoline-induced Prinzmetal angina. "Heartache" instead of headache].	2004 Jan 4	15222138
Prolongevity medicine: Antagonic-Stress drug in distress, geriatrics, and related diseases. II. Clinical review--2003.	2004 Jun	15247054
Nicergoline enhances glutamate uptake via glutamate transporters in rat cortical synaptosomes.	2004 Jun	15187425
Treatment of vascular dementia: evidence from trials with non-cholinergic drugs.	2004 Nov 15	15537523
Nicergoline reverts haloperidol-induced loss of detoxifying-enzyme activity.	2004 Nov 28	15556144
[Effect of non-selective alpha-adrenergic receptor antagonist nicergoline on the activity of neurons in the ventral lateral thalamic nucleus].	2005	16201147
[A case of pseudotumorous course of brain demyelinating disease].	2005	15822744
Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes.	2005 Dec 20	16325157
Nicergoline, a drug used for age-dependent cognitive impairment, protects cultured neurons against beta-amyloid toxicity.	2005 Jun 14	15882840
Differential modulation of microglia superoxide anion and thromboxane B2 generation by the marine manzamines.	2005 Mar 11	15762999
A phylogenetic survey of biliary lipids in vertebrates.	2005 Oct	16061950
An efficient separation and method development for the quantifying of two basic impurities of Nicergoline by reversed-phase high performance liquid chromatography using ion-pairing counter ions.	2006 Oct 11	16766155
[Influence of arterial hypertension on the clinical course of Parkinson's disease (PD) among middle-aged patients].	2007 Jul-Sep	18416166
Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics.	2007 Jun	19300564
Therapeutic use of nicergoline.	2008	18666801
Method development and validation for the simultaneous determination of cinnarizine and co-formulated drugs in pharmaceutical preparations by capillary electrophoresis.	2008 Feb 13	18164891
Second-derivative synchronous fluorescence spectroscopy for the simultaneous determination of cinnarizine and nicergoline in pharmaceutical preparations.	2008 Mar-Apr	18476347
Smart stability-indicating spectrophotometric methods for determination of binary mixtures without prior separation.	2008 Mar-Apr	18476341
Disruption of GM2/GD2 synthase gene resulted in overt expression of 9-O-acetyl GD3 irrespective of Tis21.	2008 May	18194438
Amyloid precursor protein 96-110 and beta-amyloid 1-42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids.	2008 Nov-Dec	18565728
Effects of nicergoline on corneal epithelial wound healing in rat eyes.	2009 Feb	18836171
Sertraline-induced rhabdomyolysis in an elderly patient with dementia and comorbidities.	2009 Jul	19567656
[Glaucoma--neurodegenerative disease].	2009 Oct-Dec	20191885
A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955-2008) that were completed, but not published in full.	2010 Apr 22	20412562
Nicergoline increases serum substance P levels in patients with an ischaemic stroke.	2010 Jan	20029189
Norepinephrine enhances the LPS-induced expression of COX-2 and secretion of PGE2 in primary rat microglia.	2010 Jan 11	20064241
Colloid formation by drugs in simulated intestinal fluid.	2010 May 27	20426472

Patents

Sample Use Guides

In Vivo Use Guide

5-10 mg (1-2 tablets or 20-40 drops) 3 times daily at regular intervals over prolonged periods of time. To facilitate absorption, take this medicine between meals.

Route of Administration: Oral

In Vitro Use Guide

The ability of the antidementia agent, nicergoline, to stimulate PKC mediated alpha-secretase amyloid precursor protein (APP) processing in cultured human neuroblastoma SH-SY5Y cells was investigated. Western immunoblotting of cell conditioned media using the Mabs 22C11 and 6E10 revealed the presence of 2 bands with molecular mass of 90 and 120 kDa, corresponding to possible alternatively glycosylated forms of secreted APP (APPs). Short-term (30 min and 2 h) treatment of cells with nicergoline gave an increased intensity of both bands, compared to non-treated cells. Maximal nicergoline effects, of the order of 150-200% over basal APPs release, were seen at concentrations between 1 and 10 microM. 2 h treatment with nicergoline had no effect on cellular full-length APP levels. Immunoblotting with PKC isoform specific antibodies of soluble and membrane fractions prepared from 2 h treated cells, showed that nicergoline (50 microM) induced translocation of PKC alpha, gamma and epsilon, but not PKC beta. These results indicate that nicergoline can modulate alpha-secretase APP processing by a PKC dependent mechanism that is likely to involve the gamma and epsilon isoforms of this enzyme.

Name

Type

Language

NICERGOLINE

Official Name

English

SERMION

Preferred Name

English

VASOSPAN

Brand Name

English

NSC-150531

Code

English

CERGODUM

Brand Name

English

Nicergoline [WHO-DD]

Common Name

English

nicergoline [INN]

Common Name

English

NICERGOLINE [MART.]

Common Name

English

ERGOLINE-8-METHANOL, 10-METHOXY-1,6-DIMETHYL-, (8.BETA.)-, 5-BROMO-3-PYRIDINECARBOXYLATE (ESTER)

Common Name

English

DURACEBROL

Brand Name

English

ERGOBEL

Brand Name

English

NICERGOLINE [JAN]

Common Name

English

MEMOQ

Brand Name

English

ERGOTOP

Brand Name

English

NICERGOLINE [MI]

Common Name

English

FI-6714

Code

English

NICERGOLINE [EP MONOGRAPH]

Common Name

English

10-Methoxy-1,6-dimethylergoline-8?-methanol 5-bromonicotinate (ester)

Common Name

English

NILOGRIN

Brand Name

English

CIRCO-MAREN

Brand Name

English

DILASENIL

Brand Name

English

NICERGOLENT

Brand Name

English

NICERGOLINE [USAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C04AE02