DIHYDROERGOCRISTINE MESYLATE

US Previously Marketed

First approved in 1951

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C35H41N5O5.CH4O3S
Molecular Weight	707.836
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of DIHYDROERGOCRISTINE MESYLATE

Structure Search

SMILES

CS(O)(=O)=O.[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=SPXACGZWWVIDGR-SPZWACKZSA-N

InChI=1S/C35H41N5O5.CH4O3S/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;1-5(2,3)4/h4-7,9-12,18,20,23,25,27-29,36,44H,8,13-17,19H2,1-3H3,(H,37,41);1H3,(H,2,3,4)/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
Bioavailability and pharmacokinetic profile of dihydroergotoxine from a tablet and from an oral solution formulation.	2001 Jan	11215321
Effects of topical natural ergot alkaloids on intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits.	2002 Feb	11858614
Spinal gabapentin and antinociception: mechanisms of action.	2003 Apr	12692425
Pharmacokinetics of dihydroergocristine and its major metabolite 8'-hydroxy-dihydroergocristine in human plasma.	2005 Dec	16379666
[Milestones of cardiovascular therapy. IV. Reserpine].	2007	17722843
Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results.	2008 Jan	17941060
Inappropriate medication use and risk of falls--a prospective study in a large community-dwelling elderly cohort.	2009 Jul 23	19627577
High-performance liquid chromatographic determination of dihydroergocristine in a pharmaceutical formulation with fluorescence detection.	2010 Jan-Feb	20334170
Roles of adenosine and serotonin receptors on the antinociception of sildenafil in the spinal cord of rats.	2010 Nov	20879067

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 MESYLATE

Common Name

English

DIHYDROERGOCRISTINE METHANESULFONATE

Common Name

English

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

Common Name

English

9,10-DIHYDROERGOCRISTINE METHANESULPHONATE

Common Name

English

DIHYDROERGOCRISTINE MESYLATE [VANDF]

Common Name

English

5'.ALPHA.-BENZYL-9,10.ALPHA.-DIHYDRO-12'-HYDROXY-2'-ISOPROPYLERGOTAMAN-3',6',18-TRIONE MONOMETHANESULPHONATE

Common Name

English

9,10-DIHYDROERGOCRISTINE METHANESULFONATE

Common Name

English

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

Common Name

English

DIHYDROERGOCRISTINE MESILATE [EP MONOGRAPH]

Common Name

English

Dihydroergocristine mesilate [WHO-DD]

Common Name

English

DIHYDROERGOCRISTINE METHANESULFONATE [MI]

Common Name

English

DIHYDROERGOCRISTINE MONOMESYLATE

Common Name

English

DIHYDROERGOCRISTINE MESILATE [MART.]

Common Name

English

DIHYDROERGOCRISTINE MESILATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713