LISURIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H26N4O
Molecular Weight	338.4466
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CC)C(=O)N[C@@H]1CN(C)[C@@H]2CC3=CNC4=CC=CC(=C34)C2=C1

InChI

InChIKey=BKRGVLQUQGGVSM-KBXCAEBGSA-N

InChI=1S/C20H26N4O/c1-4-24(5-2)20(25)22-14-10-16-15-7-6-8-17-19(15)13(11-21-17)9-18(16)23(3)12-14/h6-8,10-11,14,18,21H,4-5,9,12H2,1-3H3,(H,22,25)/t14-,18+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://link.springer.com/chapter/10.1007%2F978-94-015-1308-1_61
Curator's Comment: description was created based on several sources, including http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf | https://www.ncbi.nlm.nih.gov/mesh/68008090

Lisuride (DOPERGIN®), a highly active dopaminergic ergot derivative with prolactin-lowering properties, has a pronounced affinity for dopamine receptors. It may also act as an agonist at some serotonin receptors. Lisuride (DOPERGIN®) is concentrated within the pituitary where it acts on dopamine receptors which inhibit prolactin release. It can be used in the clinical conditions where a dopaminergic or prolactin-lowering effect is needed.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D1 receptor 106 Target ID: CHEMBL2056 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2752	7.19 null [pKi]
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2752	9.47 null [pKi]
Dopamine D3 receptor 97 Target ID: CHEMBL234 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2752	9.55 null [pKi]
Dopamine D4 receptor 76 Target ID: CHEMBL219 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2752	8.34 null [pKi]
Dopamine D5 receptor 15 Target ID: CHEMBL1850 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2752	8.45 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Parkinson's disease 232 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Primary	Approved 8583	DOPERGIN Approved Use As a Dopamine Agonist in: * Parkinson's disease, postencephalitic parkinsonism, parkinsonism of other origin (with the exception of the medicine-induced form) As a Prolactin Inhibitor in: * Prevention of the onset of lactation in the puerperium (primary ablactation) only for clearly defined medical reasons * Galactorrhea; prolactin-induced amenorrhea; prolactin-induced infertility in women; prolactinomas * Acromegaly
Lactation 2 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Preventing	Approved 8583	DOPERGIN Approved Use As a Dopamine Agonist in: * Parkinson's disease, postencephalitic parkinsonism, parkinsonism of other origin (with the exception of the medicine-induced form) As a Prolactin Inhibitor in: * Prevention of the onset of lactation in the puerperium (primary ablactation) only for clearly defined medical reasons * Galactorrhea; prolactin-induced amenorrhea; prolactin-induced infertility in women; prolactinomas * Acromegaly
Galactorrhea 2 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Primary	Approved 8583	DOPERGIN Approved Use As a Dopamine Agonist in: * Parkinson's disease, postencephalitic parkinsonism, parkinsonism of other origin (with the exception of the medicine-induced form) As a Prolactin Inhibitor in: * Prevention of the onset of lactation in the puerperium (primary ablactation) only for clearly defined medical reasons * Galactorrhea; prolactin-induced amenorrhea; prolactin-induced infertility in women; prolactinomas * Acromegaly
Postencephalitic parkinsonism 7 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Primary	Approved 8583	DOPERGIN Approved Use As a Dopamine Agonist in: * Parkinson's disease, postencephalitic parkinsonism, parkinsonism of other origin (with the exception of the medicine-induced form) As a Prolactin Inhibitor in: * Prevention of the onset of lactation in the puerperium (primary ablactation) only for clearly defined medical reasons * Galactorrhea; prolactin-induced amenorrhea; prolactin-induced infertility in women; prolactinomas * Acromegaly
Prolactin-induced amenorrhea 2 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Primary	Approved 8583	DOPERGIN Approved Use As a Dopamine Agonist in: * Parkinson's disease, postencephalitic parkinsonism, parkinsonism of other origin (with the exception of the medicine-induced form) As a Prolactin Inhibitor in: * Prevention of the onset of lactation in the puerperium (primary ablactation) only for clearly defined medical reasons * Galactorrhea; prolactin-induced amenorrhea; prolactin-induced infertility in women; prolactinomas * Acromegaly

C_max

Value	Dose	Analyte	Population
450 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6532807/	25 μg single, intravenous dose: 25 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
280 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6532807/	200 μg single, intravenous dose: 200 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
307 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, intravenous dose: 25 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
184 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, intramuscular dose: 25 μg route of administration: Intramuscular experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
180 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, subcutaneous dose: 25 μg route of administration: Subcutaneous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
450 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6532807/	25 μg single, intravenous dose: 25 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
730 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6532807/	200 μg single, intravenous dose: 200 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
363 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, intravenous dose: 25 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
321 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, intramuscular dose: 25 μg route of administration: Intramuscular experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
326 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, subcutaneous dose: 25 μg route of administration: Subcutaneous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
170 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6532807/	25 μg single, intravenous dose: 25 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, intravenous dose: 25 μg route of administration: Intravenous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, intramuscular dose: 25 μg route of administration: Intramuscular experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2050175/	25 μg single, subcutaneous dose: 25 μg route of administration: Subcutaneous experiment type: SINGLE co-administered:	LISURIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
34% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6532807/			LISURIDE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
2.4 mg 1 times / day steady-state, oral MTD Dose: 2.4 mg, 1 times / day Route: oral Route: steady-state Dose: 2.4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7241162/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7241162/	DLT: Psychiatric events... Dose limiting toxicities: Psychiatric events (6 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/7241162/
10 mg single, oral Overdose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/23723628/	healthy, CHILD Health Status: healthy Age Group: CHILD Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23723628/	Other AEs: hypotensia, drowsiness... Other AEs: hypotensia (1 pt) drowsiness (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/23723628/

AEs

AE	Significance	Dose	Population
Psychiatric events	6 patients DLT	2.4 mg 1 times / day steady-state, oral MTD Dose: 2.4 mg, 1 times / day Route: oral Route: steady-state Dose: 2.4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7241162/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7241162/
drowsiness	1 pt	10 mg single, oral Overdose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/23723628/	healthy, CHILD Health Status: healthy Age Group: CHILD Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23723628/
hypotensia	1 pt	10 mg single, oral Overdose Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/23723628/	healthy, CHILD Health Status: healthy Age Group: CHILD Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23723628/

PubMed

Title	Date	PubMed
Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification.	1992	1350058
High-affinity agonist binding correlates with efficacy (intrinsic activity) at the human serotonin 5-HT2A and 5-HT2C receptors: evidence favoring the ternary complex and two-state models of agonist action.	1999 May	10217294
Atypical polypoid adenomyoma in a patient with hyperprolactinemia.	2001 Jul-Aug	11520375
Dopamine partial agonist reverses amphetamine withdrawal in rats.	2001 Nov	11682262
Dopaminergic modulation of grooming behavior in virgin and pregnant rats.	2001 Nov	11668358
DA agonists -- ergot derivatives: lisuride: management of Parkinson's disease.	2002	12211144
Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease.	2002	11978145
[Results of treatment for male prolactinomas].	2002 Dec	12491580
Protection of dopaminergic neurons in primary culture by lisuride.	2002 Feb	12075855
Lisuride, a dopamine D2 receptor agonist, and anticraving drug expectancy as modifiers of relapse in alcohol dependence.	2002 Feb	11817496
Clustered ergot alkaloids modulate cell-mediated cytotoxicity.	2002 Feb	11741789
Terguride treatment attenuated prolactin release and enhanced insulin receptor affinity and GLUT 4 content in obese spontaneously hypertensive female, but not male rats.	2002 Jun	12079879
Sleep attacks in patients taking dopamine agonists: review.	2002 Jun 22	12077032
Characterization of phospholipase C activity at h5-HT2C compared with h5-HT2B receptors: influence of novel ligands upon membrane-bound levels of [3H]phosphatidylinositols.	2002 Mar	11882920
5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens.	2002 May	11900766
An evidence-based review of dopamine receptor agonists in the treatment of Parkinson's disease.	2002 Oct	12436117
Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats.	2002 Oct	12373423
Differential activation of Gq/11 and Gi(3) proteins at 5-hydroxytryptamine(2C) receptors revealed by antibody capture assays: influence of receptor reserve and relationship to agonist-directed trafficking.	2002 Sep	12181434
Effects of a partial dopamine D2-like agonist on the cocaine-induced behavioral sensitization of preweanling rats.	2003 Aug	13679214
Cortisol as an indicator of dopaminergic effects on nicotine craving.	2003 Aug	12923821
The dopamine receptor agonist lisuride attenuates iron-mediated dopaminergic neurodegeneration.	2003 Nov	14637122
Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum.	2003 Oct	14523624
Management of restless legs syndrome by the partial D2-agonist terguride.	2003 Sep	14592288
Effects of terguride treatment on glucose abnormalities induced by ischemic brain damage in SHR/N-cp lean Koletsky strain and in rats of Wistar strain.	2004	15658573
Pharmacology of polymorphic variants of the human 5-HT1A receptor.	2004 Feb 1	15037200
LSD, 5-HT (serotonin), and the evolution of a behavioral assay.	2004 Jan	15019419
Evidence for the management of mastalgia.	2004 May	15140333
Regulation of serotonin 5-HT2C receptors by chronic ligand exposure.	2004 Sep 13	15363976
Mastalgia: a review of management.	2005 Dec	16444894
Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.	2005 May	15818599
Levodopa in the treatment of Parkinson's disease: current controversies.	2005 May	15732130
Pharmacokinetic optimisation in the treatment of Parkinson's disease : an update.	2006	16485914
Effects of a partial D2-like receptor agonist on striatal dopamine autoreceptor functioning in preweanling rats.	2006 Feb 16	16427034
Lisuride treatment of restless legs syndrome: first studies with monotherapy in de novo patients and in combination with levodopa in advanced disease.	2006 Jan	16372146
Homology modelling of the serotoninergic 5-HT2c receptor.	2006 Jun	16918076
Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat.	2006 Mar	16647107
The partial dopamine D2-like receptor agonist terguride functions as an agonist in preweanling rats after a 5-day reserpine regimen.	2006 Mar	16447063
Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.	2006 Mar 27	16545797
Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis.	2006 Mar-Apr	16614540
Glutamate-induced cell death and formation of radicals can be reduced by lisuride in mesencephalic primary cell culture.	2006 Sep	16463121

Patents

Sample Use Guides

In Vivo Use Guide

Parkinsonism: The treatment begins with half of a 0.2 mg DOPERGIN® tablet (0.1 mg) in the evening and should be increased by 0.1 mg weekly until a clinical effect becomes apparent. Endocrine Indications: One DOPERGIN® 0.2 mg tablet should be taken 2 to 3 times daily for 14 days.

Route of Administration: Oral

In Vitro Use Guide

Lysergic acid diethylamide (LSD) and lisuride were potent partial agonists at 5HT2A receptors with EC50 values of 7.2 nM and 17 nM, respectively. Also, LSD and lisuride were partial agonists at 5HT2C receptors with EC50 values of 27 nM and 94 nM, respectively.

Name

Type

Language

LISURIDE

Official Name

English

LISURIDE [MI]

Preferred Name

English

Lisuride [WHO-DD]

Common Name

English

LYSURIDE

Common Name

English

lisuride [INN]

Common Name

English

3-(9,10-DIDEHYDRO-6-METHYLERGOLIN-8.ALPHA.-YL)-1,1-DIETHYLUREA

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

316610