METERGOLINE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H29N3O2
Molecular Weight	403.5167
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=C2C[C@@H]3[C@H](C[C@@H](CNC(=O)OCC4=CC=CC=C4)CN3C)C5=CC=CC1=C25

InChI

InChIKey=WZHJKEUHNJHDLS-QTGUNEKASA-N

InChI=1S/C25H29N3O2/c1-27-14-18(13-26-25(29)30-16-17-7-4-3-5-8-17)11-21-20-9-6-10-22-24(20)19(12-23(21)27)15-28(22)2/h3-10,15,18,21,23H,11-14,16H2,1-2H3,(H,26,29)/t18-,21+,23+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB13520
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11910270 | https://www.ncbi.nlm.nih.gov/pubmed/12411222 | https://www.ncbi.nlm.nih.gov/pubmed/27251511 | https://www.ncbi.nlm.nih.gov/pubmed/8650684 |

Metergoline is a psychoactive drug of the ergoline chemical class which acts as a ligand for various serotonin and dopamine receptors. Metergoline is an antagonist at various 5-HT receptor subtypes at a relatively low concentration and an agonist at dopamine receptors. Its use has been studied in various clinical settings such as a treatment for seasonal affective disorder, prolactin hormone regulation due to its inhibitory effect on prolactin release premenstrual dysphoric disorder in women and antianxiety treatment

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20451398	Agonist 2752	74.0 nM [Ki]
Serotonin 1d (5-HT1d) receptor 53 Target ID: CHEMBL1983 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20451398	Antagonist 2849	0.9 nM [Ki]
Serotonin 2b (5-HT2b) receptor 60 Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20451398	Antagonist 2849	2.6 nM [Ki]
Muscarinic acetylcholine receptor M3 160 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20451398	Antagonist 2849	3.8 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Major depressive disorder 179 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11910270	Primary	Not Provided 511	Unknown Approved Use Unknown
Premenstrual dysphoric disorder 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12411222	Primary	Not Provided 511	Unknown Approved Use Unknown
Pseudopregnancy 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8650684	Primary	Not Provided 511	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
5-hydroxy-L-tryptophan Suppressed Food Intake in Rats Despite an Increase in the Arcuate NPY Expression.	2010-12	22110352
On the mechanism of the antidepressant-like action of group II mGlu receptor antagonist, MGS0039.	2010-12	20703449
Evaluation of [(11)C]metergoline as a PET radiotracer for 5HTR in nonhuman primates.	2010-11-15	20451398
In vitro synergistic effects of metergoline and antifungal agents against Candida krusei.	2010-11	19538518
On the intrinsic regulation of neuropeptide Y release in the mammalian suprachiasmatic nucleus circadian clock.	2010-03	20377624
A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test.	2010-02	19945477
Tonic serotonergic control of ingestive behaviours in the pigeon (Columba livia): the role of the arcopallium.	2009-12-28	19632276
Antidepressant-like effects of glucagon-like peptide-2 in mice occur via monoamine pathways.	2009-12-01	19539656
cis-Urocanic acid stimulates primary human keratinocytes independently of serotonin or platelet-activating factor receptors.	2009-11	19474802
The bovine mammary gland expresses multiple functional isoforms of serotonin receptors.	2009-10	19654143
Human 5-HT7 receptor-induced inactivation of forskolin-stimulated adenylate cyclase by risperidone, 9-OH-risperidone and other "inactivating antagonists".	2009-09	19509219
Serotonergic-postsynaptic receptors modulate gripping-induced immobility episodes in male taiep rats.	2009-09	19484723
Pharmacological analysis of the novel, rapid, and potent inactivation of the human 5-Hydroxytryptamine7 receptor by risperidone, 9-OH-Risperidone, and other inactivating antagonists.	2009-02	18996971
Panic disorder: is the PAG involved?	2009	19283082
Selective serotonin reuptake inhibitors: a review of its effects on intraocular pressure.	2008-12	19587851
The effects of metergoline and 8-OH-DPAT injections into arcuate nucleus and lateral hypothalamic area on feeding in female rats during the estrous cycle.	2008-10-20	18694771
The structure of human serotonin 2c G-protein-coupled receptor bound to agonists and antagonists.	2008-08	18499489
Physiology of the canine anoestrus and methods for manipulation of its length.	2008-07	18638118
Possible involvement of endogenous 5-HT in aggravation of cerulein-induced acute pancreatitis in mice.	2007-11	17965538
Anxiolytic-like action of MTEP expressed in the conflict drinking Vogel test in rats is serotonin dependent.	2007-11	17870136
In vivo Schild regression analyses using nonselective 5-HT2C receptor antagonists in a rat operant behavioral assay.	2007-08	17401722
Feeding behavior after metergoline or GR-46611 injections into the paraventricular nucleus of the hypothalamus in the pigeon.	2007-05-16	17360049
Anxiolytic-like effect of group III mGlu receptor antagonist is serotonin-dependent.	2007-02	17020774
Serotonin increases the phase shift of the circadian locomotor activity rhythm in mice after dark pulses in constant light conditions.	2007	18274252
Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HT1A and 5-HT2 receptors in the spinal cord.	2006-11	16921395
Reanalysis of constitutively active rat and human 5-HT7(a) receptors in HEK-293F cells demonstrates lack of silent properties for reported neutral antagonists.	2006-10	16967291
Dopamine agonists, anti-progestins, anti-androgens, long-term-release GnRH agonists and anti-estrogens in canine reproduction: a review.	2006-10	16542717
Anoestrus in the dog: a fascinating story.	2006-08	16869884
Serotonergic mediation of constant light-potentiated nonphotic phase shifting of the circadian locomotor activity rhythm in Syrian hamsters.	2006-07	16760334
Effects of dopamine D1-like receptor agonists on food-maintained operant behavior in rats.	2006-06	16914948
Clozapine modulates aromatic L-amino acid decarboxylase activity in mouse striatum.	2006-05	16415089
Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.	2006-03-27	16545797
Selective and nonselective serotonin antagonists block the aversive stimulus properties of MK212 and m-chlorophenylpiperazine (mCPP) in mice.	2005-12	16165167
5-HT1B receptors modulate the feeding inhibitory effects of enterostatin.	2005-11-16	16256085
Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder.	2005-09	18568072
Treatment of seasonal affective disorders.	2003-12	22033639
Gonadal steroids, brain, and behavior: role of context.	2002-06	22033695
Reproductive hormonal treatments for mood disorders in women.	2002-06	22033644
Cloning and characterisation of the human 5-HT5A serotonin receptor.	1994-12-05	7988681
Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase.	1993-11-05	8226867
Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs.	1993-03	7680751
Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.	1993-01-15	8380639
Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype.	1992-06-15	1608964
Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor.	1991-08	1652050
Effect of metergoline, fenfluramine, and 8-OHDPAT on catalepsy induced by haloperidol or morphine.	1988-08	2972934
Antagonism of drug-induced yawning and penile erections in rats.	1986-03-18	2872065
Pharmacology in vivo of the phenylindan derivative, Lu 19-005, a new potent inhibitor of dopamine, noradrenaline and 5-hydroxytryptamine uptake in rat brain.	1985-04	2409454
Central antiserotonergic and antidopaminergic action of pirenperone, a putative 5-HT2 receptor antagonist.	1985-03-01	4048012
The influence of 5-HT receptor blocking agents on the behavioral effects of analgesics in rats.	1980	6771831
Determination of the role of serotonergic and cholinergic systems in apomorphine--induced aggressiveness in rats.	1979-03-01	573894

Patents

Sample Use Guides

In Vivo Use Guide

from 7.5 mg/day to 40 mg/day

Route of Administration: Oral

In Vitro Use Guide

Oocytes were injected with human Kv1.4 channel cRNAs and maintained for 2 to 4 d before Kv1.4 channel currents were recorded in ND96 using a two-electrode voltage clamp technique. Original K+ current traces are shown under control conditions, after bath superfusion of metergoline and washout. Voltage pulses of 500-ms duration were applied in 10-mV increments and at 10-s intervals from a holding potential of –80 mV. I–V relationships of human Kv1.4 channels were recorded in the absence or presence of 10 μM metergoline (MG). The current-voltage relationships of Kv1.4 channels were obtained using voltage steps between –80 and +60 mV taken in 10 mV increments.

Name

Type

Language

METERGOLINE

Official Name

English

FI 6337

Preferred Name

English

NSC-755878

Code

English

FI-6337

Code

English

(+)-N-(CARBOXY)-1-METHYL-9,10-DIHYDROLYSERGAMINE BENZYL ESTER

Common Name

English

METERGOLINE [MI]

Common Name

English

metergoline [INN]

Common Name

English

METERGOLINE [MART.]

Common Name

English

MCE

Code

English

Metergoline [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884