DIHYDROERGOCORNINE

US Previously Marketed

First approved in 1951

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H41N5O5
Molecular Weight	563.6877
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CCCN1C(=O)[C@H](C(C)C)N3C(=O)[C@](NC(=O)[C@H]4CN(C)[C@]5([H])CC6=CNC7=C6C(=CC=C7)[C@@]5([H])C4)(O[C@@]23O)C(C)C

InChI

InChIKey=SEALOBQTUQIVGU-QNIJNHAOSA-N

InChI=1S/C31H41N5O5/c1-16(2)26-28(38)35-11-7-10-24(35)31(40)36(26)29(39)30(41-31,17(3)4)33-27(37)19-12-21-20-8-6-9-22-25(20)18(14-32-22)13-23(21)34(5)15-19/h6,8-9,14,16-17,19,21,23-24,26,32,40H,7,10-13,15H2,1-5H3,(H,33,37)/t19-,21-,23-,24+,26+,30-,31+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/cdi/hydergine.html
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/2869188 | https://www.ncbi.nlm.nih.gov/pubmed/4205319 | https://www.ncbi.nlm.nih.gov/pubmed/14350151 | https://www.ncbi.nlm.nih.gov/pubmed/17941060

Dihydroergocornine is an ergot alkaloid, one of the three components of ergoloid (trade name Hydergine). Dihydroergocornine (as the component of Ergoloid mesylates) has been used to treat dementia and age-related cognitive impairment (such as in Alzheimer disease), as well as to aid in recovery after stroke. There is no specific evidence which clearly establishes the mechanism by which Hydergine® (ergoloid mesylates) preparations produce mental effects, nor is there conclusive evidence that the drug particularly affects cerebral arteriosclerosis or cerebrovascular insufficiency. Hydergine may stimulates dopaminergic and serotonergic receptors and blocks alpha-adrenoreceptors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2869188	Antagonist 2778
Dopamine D1 receptor 101 Target ID: CHEMBL265 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2869188	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Vascular dementia 11 Sources: https://clinicaltrials.gov/ct2/show/NCT01475578	Primary	Phase II 1132	Hydergine Approved Use Unknown Launch Date 1977
Dementia 27 Sources: https://www.drugs.com/pro/hydergine.html	Primary	Approved 8429	Hydergine Approved Use Unknown Launch Date 1977
Alzheimer’s disease 272 Sources: https://www.drugs.com/pro/hydergine.html	Primary	Approved 8429	Hydergine Approved Use Unknown Launch Date 1977

C_max

Value	Dose	Analyte	Population
0.04 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17941060/	27 mg single, oral dose: 27 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROERGOCRISTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.04 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17941060/	27 mg single, oral dose: 27 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROERGOCRYPTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.04 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17941060/	27 mg single, oral dose: 27 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROERGOCORNINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.98 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17941060/	27 mg single, oral dose: 27 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROXY-DIHYDROERGOCORNIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.53 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17941060/	27 mg single, oral dose: 27 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROXY-DIHYDROERGOCRYPTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.3 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17941060/	27 mg single, oral dose: 27 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROXY-DIHYDROERGOCRISTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:59909	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:59909
ZINC	ZINC000004215648	http://zinc15.docking.org/substances/ZINC000004215648

PubMed

Title	Date	PubMed
The treatment of minocycline-induced brainstem vertigo by the combined administration of piracetam and ergotoxin.	1989	2635498
Bioavailability and pharmacokinetic profile of dihydroergotoxine from a tablet and from an oral solution formulation.	2001 Jan	11215321
Placebo adverse events in headache trials: headache as an adverse event of placebo.	2003 Sep	12950374
Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat.	2007 Apr	17497262
Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results.	2008 Jan	17941060

Patents

Sample Use Guides

In Vivo Use Guide

1 mg of ergoloid mesylates three times daily. 1 mg of ergoloid mesylates contains: dihydroergocornine mesylate 0.333 mg, dihydroergocristine mesylate 0.333 mg, and dihydroergocryptine (dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine in the proportion of 2:1) mesylate 0.333 mg,

Route of Administration: Oral

In Vitro Use Guide

Biotransformation assays were performed in incubates of rat liver microsomes. Dihydroergotoxine alkaloids in CH3CN–H2O (1:1, v/v) were individually added (30 mm, final concentration) to cold Sorensen buffer 0.1 m pH 7.4 containing the liver enzyme preparation (5mgprot/ml), MgCl2 (10mm), glucose 6-phosphate (10mm), NADP (0.5mm) and glucose 6-phosphate dehydrogenase (1 U/ml) in a total volume of 500 ml. Blank and control incubates were performed similarly, except by adding the buffer solution instead of the drug and NADPH regenerating system, respectively. After incubation at 378C for 30 min, the reactions were terminated by the addition of 50 ml NaOH 0.1m, and vortex-mixing (30 s) with 4ml of diethyl ether. After 15 min at -80C, the upper organic layers were separated and concentrated under a gentle N2 stream.

Name

Type

Language

DIHYDROERGOCORNINE

Common Name

English

9,10-DIHYDROERGOCORNINE

Common Name

English

ERGOTAMAN-3',6',18-TRIONE, 9,10-DIHYDRO-12'-HYDROXY-2',5'-BIS(1-METHYLETHYL)-, (5'ALPHA,10ALPHA)-

Common Name

English

Dihydroergocornine [WHO-DD]

Common Name

English

DIHYDROERGOCORNINE [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884