MESULERGINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H26N4O2S
Molecular Weight	362.49
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC3=CN(C)C4=CC=CC(=C34)[C@@]1([H])C[C@@H](CN2C)NS(=O)(=O)N(C)C

InChI

InChIKey=JLVHTNZNKOSCNB-YSVLISHTSA-N

InChI=1S/C18H26N4O2S/c1-20(2)25(23,24)19-13-9-15-14-6-5-7-16-18(14)12(10-21(16)3)8-17(15)22(4)11-13/h5-7,10,13,15,17,19H,8-9,11H2,1-4H3/t13-,15+,17+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3517235 | https://www.ncbi.nlm.nih.gov/pubmed/6855451

Mesulergine, an antagonist of 5-HT2C, and dopamine receptors was studied in clinical trials for the treatment of Parkinson's disease. However, further, development was discontinued due to toxicological observations in animal experiments.

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 2a (5-HT2a) receptor 231 Target ID: CHEMBL322 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7938165	Antagonist 2778	2.0 nM [Ki]
Serotonin 2c (5-HT2c) receptor 124 Target ID: CHEMBL324 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27061981	Antagonist 2778	1.9 nM [Ki]
Dopamine D2 receptor 297 Target ID: CHEMBL339 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6230246\|https://www.ncbi.nlm.nih.gov/pubmed/12648304\|https://www.ncbi.nlm.nih.gov/pubmed/6468500\|https://www.ncbi.nlm.nih.gov/pubmed/10650171	Partial Agonist 290	8.0 nM [Ki]

PubMed

Title	Date	PubMed
The effect of serotonergic agents on haloperidol-induced catalepsy.	1990	2250574
Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase.	1993 Aug	8394987
Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype.	1993 Aug 25	8394362
Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor.	1993 Mar	8450835
Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase.	1993 Nov 5	8226867
Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b).	1997 Sep	9298538
Functional characterisation of the human cloned 5-HT7 receptor (long form); antagonist profile of SB-258719.	1998 Jul	9720804
The 5-hydroxytryptamine6 receptor-selective radioligand [3H]Ro 63-0563 labels 5-hydroxytryptamine receptor binding sites in rat and porcine striatum.	1998 Sep	9730917
5-HT1A and 5-HT2 receptors differentially regulate the excitability of 5-HT-containing neurones of the guinea pig dorsal raphe nucleus in vitro.	2001 Apr 27	11311877
Pharmacological characterisation of human 5-HT2 receptor subtypes.	2001 Feb 23	11230991
Multiple conformations of native and recombinant human 5-hydroxytryptamine(2a) receptors are labeled by agonists and discriminated by antagonists.	2001 Oct	11562430
5-HT7 receptor-mediated relaxation of the oviduct in nonpregnant proestrus pigs.	2003 Feb 14	12586216
Further evidence that the discriminative stimulus properties of indorenate are mediated by 5-HT 1A/1B/2C receptors.	2003 Jan	12479957
Pharmacological characterization of a serotonin receptor (5-HT7) stimulating cAMP production in human corneal epithelial cells.	2003 Nov	14578406
Kv1.1 and Kv1.3 channels contribute to the delayed-rectifying K+ conductance in rat choroid plexus epithelial cells.	2004 Mar	14602579
Involvement of 5-hydroxytryptamine (HT)7 receptors in the 5-HT excitatory effects on the rat urinary bladder.	2004 Nov	15541139
The role of the phosphatidyinositol-linked D1 dopamine receptor in the pharmacology of SKF83959.	2005 Apr	15820529
Effects of mu-CPP and mesulergine on dietary choices in deprived rats: possible mechanisms of their action.	2006 Jan	16242827
Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.	2006 Mar 27	16545797
Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor.	2008 Apr	18344975
Serotonin activates presynaptic and postsynaptic receptors in rat globus pallidus.	2008 Apr	18234984
Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulation of cell surface expression and signal transduction.	2008 Mar	18083778
Assessing the neuronal serotonergic target-based antidepressant stratagem: impact of in vivo interaction studies and knockout models.	2008 Sep	19506722
Distribution and neurochemical characterization of neurons within the nucleus of the solitary tract responsive to serotonin agonist-induced hypophagia.	2009 Jan 3	18762217
The sedating antidepressant trazodone impairs sleep-dependent cortical plasticity.	2009 Jul 1	19568418
Arylbenzazepines are potent modulators for the delayed rectifier K+ channel: a potential mechanism for their neuroprotective effects.	2009 Jun 5	19503734
Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri.	2009 Oct	19700373
Down-regulation of cerebellar 5-HT(2C) receptors in pilocarpine-induced epilepsy in rats: therapeutic role of Bacopa monnieri extract.	2009 Sep 15	19439326
Impact of RNA editing on functions of the serotonin 2C receptor in vivo.	2010	20582266
Clozapine and other competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions.	2010 Dec	20827463
Electrophysiological effects of SKF83959 on hippocampal CA1 pyramidal neurons: potential mechanisms for the drug's neuroprotective effects.	2010 Oct 1	20957037
Reversal of haloperidol-induced motor deficits by mianserin and mesulergine in rats.	2011 Jan	21190911

Sample Use Guides

In Vivo Use Guide

Initial dose were 0-5 mg mesulergine once a day. Doses were increased every 3-4 days by increments of 0-5 mg. Mesulergine the daily dose being distributed over 2-4 intakes. After the 20th day of treatment the daily dose was increased every 3-4 days by increments of 1- 0 mg, until a satisfactory therapeutic response was obtained or until significant side-effects appeared. Maximum daily doses of mesulergine was 30 mg.

Route of Administration: Oral

Name

Type

Language

MESULERGINE

Official Name

English

Mesulergine [WHO-DD]

Common Name

English

N'-(1,6-DIMETHYLERGOLIN-8.ALPHA.-YL)-N,N-DIMETHYLSULFAMIDE

Systematic Name

English

mesulergine [INN]

Common Name

English

{[(2R,4S,7R)-6,11-dimethyl-6,11-diazatetracyclo[7.6.1.0{2,7}.0{12,16}]hexadeca-1(16),9,12,14-tetraen-4-yl]sulfamoyl}dimethylamine

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884