DIHYDROERGOCRISTINE

US Previously Marketed

First approved in 1951

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C35H41N5O5
Molecular Weight	611.7305
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](CC3=CC=CC=C3)N4C(=O)[C@](NC(=O)[C@H]5CN(C)[C@]6([H])CC7=CNC8=C7C(=CC=C8)[C@@]6([H])C5)(O[C@@]24O)C(C)C

InChI

InChIKey=DEQITUUQPICUMR-HJPBWRTMSA-N

InChI=1S/C35H41N5O5/c1-20(2)34(37-31(41)23-16-25-24-11-7-12-26-30(24)22(18-36-26)17-27(25)38(3)19-23)33(43)40-28(15-21-9-5-4-6-10-21)32(42)39-14-8-13-29(39)35(40,44)45-34/h4-7,9-12,18,20,23,25,27-29,36,44H,8,13-17,19H2,1-3H3,(H,37,41)/t23-,25-,27-,28+,29+,34-,35+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/hydergine_508.pdf

Dihydroergocristine is an ergot alkaloid that has an partial agonist activity on dopaminergic and alpha-adrenergic receptors and antagonist activity on serotonin receptors. The drug was approved by FDA in combination with other alkaloids (dihydroergocornine, dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine mesylate salts) under the name Hydergine for the treatment of dimentia and cerebrovascular insufficiency.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adrenergic receptor alpha 64 Target ID: CHEMBL2095203 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Ergot_derivatives-containing_products/WC500161329.pdf	Partial Agonist 290	2.4 nM [Ki]
Dopamine receptor 60 Target ID: CHEMBL2096905 Sources: https://www.tocris.com/pdfs/dopreview.pdf	Partial Agonist 290
Serotonin (5-HT) receptor 34 Target ID: CHEMBL2096904 Sources: https://www.tocris.com/pdfs/dopreview.pdf	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dementia 27 Sources: https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/hydergine_508.pdf	Primary		Approved 8429	HYDERGINE Approved Use The treatment of senility and cerebrovascular insufficiency. Launch Date 1977
Cerebrovascular insufficiency 15 Sources: https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/hydergine_508.pdf	Primary		Approved 8429	HYDERGINE Approved Use The treatment of senility and cerebrovascular insufficiency. Launch Date 1977

C_max

Value	Dose	Co-administered	Analyte	Population
0.28 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16379666/	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		DIHYDROERGOCRISTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.63 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16379666/	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		8'-HYDROXY-DIHYDROERGOCRISTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
0.46 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16379666/	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		DIHYDROERGOCRISTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
13.36 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16379666/	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		8'-HYDROXY-DIHYDROERGOCRISTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16379666/	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		DIHYDROERGOCRISTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16379666/	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		8'-HYDROXY-DIHYDROERGOCRISTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
20 mg 1 times / day steady, oral Highest studied dose Dose: 20 mg, 1 times / day Route: oral Route: steady Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7589764/	unhealthy, 55 - 80 years n = 20 Health Status: unhealthy Condition: chronic cerebro-vascular disease Age Group: 55 - 80 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/7589764/	Other AEs: Gastric pain... Other AEs: Gastric pain (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/7589764/

AEs

AE	Significance	Dose	Population
Gastric pain	1 patient	20 mg 1 times / day steady, oral Highest studied dose Dose: 20 mg, 1 times / day Route: oral Route: steady Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7589764/	unhealthy, 55 - 80 years n = 20 Health Status: unhealthy Condition: chronic cerebro-vascular disease Age Group: 55 - 80 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/7589764/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:59912	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:59912
ZINC	ZINC000003995616	http://zinc15.docking.org/substances/ZINC000003995616

PubMed

Title	Date	PubMed
Effects of phentolamine, dihydroergocristine and isoxsuprine on the blood pressure and heart rate in normotensive, hypotensive and hypertensive rats.	1975	811997
The treatment of minocycline-induced brainstem vertigo by the combined administration of piracetam and ergotoxin.	1989	2635498
Effects of four non-cholinergic cognitive enhancers in comparison with tacrine and galanthamine on scopolamine-induced amnesia in rats.	1992	1738791

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage (in form of hydergine tablets containing dihydroergocornine, dihydroergocristine, dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine mesylate salts in an approximate weight ratio of 1:1:1) in the US is 1 mg three times daily. In Europe and Japan, up to 12 mg of hydergine daily have been used without serious adverse effects.

Route of Administration: Oral

In Vitro Use Guide

C-1300 neuroblastoma cells were incubated with dihydroergocristine at concentration of 2 uM. In another experiment dihydroergocristine was added to the perfusion medium of the isolated rat brain in a concentration of 5 uM. In both experiments the drug caused changes in the concentrations of the high-energy phosphates.

Name

Type

Language

DIHYDROERGOCRISTINE

Common Name

English

Dihydroergocristine [WHO-DD]

Common Name

English

GNF-PF-3462

Code

English

DIHYDROERGOCRISTINE [VANDF]

Common Name

English

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

Common Name

English

9,10-DIHYDROERGOCRISTINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884