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

[H][C@@]12CC3=CNC4=CC=CC(=C34)C1=C[C@@H](CN2C)NC(=O)N(CC)CC

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 101 Target ID: CHEMBL2056 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2678	7.19 null [pKi]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2678	9.47 null [pKi]
Dopamine D3 receptor 91 Target ID: CHEMBL234 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2678	9.55 null [pKi]
Dopamine D4 receptor 71 Target ID: CHEMBL219 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2678	8.34 null [pKi]
Dopamine D5 receptor 12 Target ID: CHEMBL1850 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Agonist 2678	8.45 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Parkinson's disease 226 Sources: http://www.bayerresources.com.au/resources/uploads/datasheet/file9563.pdf	Primary	Approved 8429	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 8429	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 8429	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 8429	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 8429	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

PubMed

Title	Date	PubMed
Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification.	1992	1350058
[Use of dopamine agonists in the treatment of Parkinson's disease].	2002	12378886
DA agonists -- ergot derivatives: bromocriptine: management of Parkinson's disease.	2002	12211141
Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease.	2002	11978145
Protection of dopaminergic neurons in primary culture by lisuride.	2002 Feb	12075855
Dopamine agonist and antagonist responders as related to types of nicotine craving and facets of extraversion.	2002 Jun	12369256
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
SUNCT syndrome in two patients with prolactinomas and bromocriptine-induced attacks.	2002 Jun 11	12058109
Sleep attacks in patients taking dopamine agonists: review.	2002 Jun 22	12077032
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.	2002 Nov	12388666
Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats.	2002 Oct	12373423
Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson's disease.	2002 Sep	12183351
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
Inhibition of growth hormone excess reduces insulin resistance and ovarian dysfunction in a lean case of polycystic ovary syndrome with a growth-hormone-producing pituitary adenoma.	2003	12637795
[Pharmacokinetic/pharmacodynamic analysis of anti-hyperprolactinemic effect of terguride based on dopamine D2 receptor occupancy].	2003 Apr	12704865
Cortisol as an indicator of dopaminergic effects on nicotine craving.	2003 Aug	12923821
Prevention and treatment of motor fluctuations.	2003 Aug	12915071
Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson's disease.	2003 Jun	12784269
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
Transdermal lisuride delivery in the treatment of Parkinson's disease.	2004	15354393
Pergolide, terguride and N,N'-spacer-linked oligomers of both interact with 5-HT2A receptors of rat tail artery.	2004	14984312
Pharmacology of polymorphic variants of the human 5-HT1A receptor.	2004 Feb 1	15037200
8R-lisuride is a potent stereospecific histamine H1-receptor partial agonist.	2004 Mar	14978232
Familial acromegaly: a familial report and review of the literature.	2004 May	15473133
Evidence for the management of mastalgia.	2004 May	15140333
D1 but not D2 dopamine receptors or adrenoceptors mediate dopamine-induced potentiation of N-methyl-d-aspartate currents in the rat prefrontal cortex.	2004 Nov 30	15531094
The effects of dopamine receptor agonists and antagonists on the secretory rate of cockroach (Periplaneta americana) salivary glands.	2004 Sep	15350502
Regulation of serotonin 5-HT2C receptors by chronic ligand exposure.	2004 Sep 13	15363976
Agonism at 5-HT2B receptors is not a class effect of the ergolines.	2005 Apr 25	15862804
Mastalgia: a review of management.	2005 Dec	16444894
Capillary zone electrophoresis separation of enantiomers of lisuride.	2005 Feb 25	15794580
Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats.	2005 Jan	15138444
Delineation of receptor-ligand interactions at the human histamine H1 receptor by a combined approach of site-directed mutagenesis and computational techniques - or - how to bind the H1 receptor.	2005 Jun	15952243
Dopamine and serotonin modulate the onset of metamorphosis in the ascidian Phallusia mammillata.	2005 Jun 1	15936344
Influence of steric hindrance on enantioseparation of Dns-amino acids and pesticides on terguride based chiral selectors in capillary electrophoresis.	2005 May	15912739
Levodopa in the treatment of Parkinson's disease: current controversies.	2005 May	15732130
Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic.	2005 May 16	15894311
Transdermal treatment options for neurological disorders: impact on the elderly.	2006	16823990
Pharmacokinetic optimisation in the treatment of Parkinson's disease : an update.	2006	16485914
Dopamine stimulation via infusion in the lateral ventricle.	2006 Aug	17105930
Ergoline and non-ergoline derivatives in the treatment of Parkinson's disease.	2006 Aug	16944356
Striking differences of action of lisuride stereoisomers at histamine H1 receptors.	2006 Dec	17106670
In vitro characterization of SLV308 (7-[4-methyl-1-piperazinyl]-2(3H)-benzoxazolone, monohydrochloride): a novel partial dopamine D2 and D3 receptor agonist and serotonin 5-HT1A receptor agonist.	2006 Dec 15	17001660
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
Transdermal lisuride: short-term efficacy and tolerability study in patients with severe restless legs syndrome.	2006 Jan	16194624
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
In vitro functional characteristics of dopamine D2 receptor partial agonists in second and third messenger-based assays of cloned human dopamine D2Long receptor signalling.	2007 Aug	17092971

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 [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

LISURIDE [MI]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

316610