PYRILAMINE MALEATE

US Approved OTC

First approved in 1948

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H23N3O.C4H4O4
Molecular Weight	401.4562
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.COC1=CC=C(CN(CCN(C)C)C2=CC=CC=N2)C=C1

InChI

InChIKey=JXYWFNAQESKDNC-BTJKTKAUSA-N

InChI=1S/C17H23N3O.C4H4O4/c1-19(2)12-13-20(17-6-4-5-11-18-17)14-15-7-9-16(21-3)10-8-15;5-3(6)1-2-4(7)8/h4-11H,12-14H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/cdi/phenylephrine-pyrilamine.html

Pyrilamine (also known as Mepyramine) is a first generation antihistamine, targeting the H1 receptor. However, it rapidly permeates the brain and so often causes drowsiness as a side effect. It is used in over-the-counter combination products for colds and menstrual symptoms. Mepyramine is a histamine H1 receptor inverse agonist. It binds to a G protein-coupled form of the receptor and promotes a G protein-coupled inactive state of the H1 receptor that interferes with the Gq/11-mediated signaling. Mepyramine competes with histamine for binding at H1-receptor sites on the effector cell surface, resulting in suppression of histaminic edema, flare, and pruritus. The sedative properties of Mepyramine occur at the subcortical level of the CNS. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22918191	Antagonist 2778		0.8 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Allergic rhinitis 100 Sources: https://www.drugs.com/cdi/phenylephrine-pyrilamine.html	Primary	Approved 8429	Phenylephrine/ pyrilamine Approved Use Uses Temporarily relieves nasal congestion due to hay fever (allergic rhinitis) runny nose sneezing, itching of nose or throat and itchy, watery eyes due to hay fever or upper respiratory allergies Launch Date 1982
Upper respiratory allergies 8 Sources: https://www.drugs.com/cdi/phenylephrine-pyrilamine.html	Primary	Approved 8429	Phenylephrine/ pyrilamine Approved Use Uses Temporarily relieves nasal congestion due to hay fever (allergic rhinitis) runny nose sneezing, itching of nose or throat and itchy, watery eyes due to hay fever or upper respiratory allergies Launch Date 1982
Premenstrual syndrome 37 Sources: https://www.drugs.com/drp/pyrilamine-maleate.html	Primary	Approved 8429	MIDOL PMS Approved Use Uses: For the temporary relief of these symptoms associated with menstrual periods: bloating water-weight gain cramps breast tenderness headache backache Launch Date 1982

C_max

Value	Dose	Co-administered	Analyte	Population
36.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19161458/	300 mg single, intravenous dose: 300 mg route of administration: Intravenous experiment type: SINGLE co-administered:		PYRILAMINE plasma	Equus caballus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
54.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19161458/	300 mg single, intravenous dose: 300 mg route of administration: Intravenous experiment type: SINGLE co-administered:		PYRILAMINE plasma	Equus caballus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19161458/	300 mg single, intravenous dose: 300 mg route of administration: Intravenous experiment type: SINGLE co-administered:		PYRILAMINE plasma	Equus caballus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg single, oral Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8079504/	healthy, 32-38 years n = 3 Health Status: healthy Age Group: 32-38 years Sex: M Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/8079504/	Sources: https://pubmed.ncbi.nlm.nih.gov/8079504/
0.3 % 1 times / day steady, ophthalmic Recommended Dose: 0.3 %, 1 times / day Route: ophthalmic Route: steady Dose: 0.3 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1687324/	unhealthy, adult Health Status: unhealthy Condition: Allergic conjunctivitis Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/1687324/	Sources: https://pubmed.ncbi.nlm.nih.gov/1687324/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	OCTN2 50

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/7853212/	yes [IC50 0.034 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OCTN2 50	substrate 3367 Sources: https://onlinelibrary.wiley.com/doi/abs/10.1002/bdd.681	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/16278312/ Page: 3.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY579206	https://www.001chemical.com/chem/91-84-9
3B Scientific (Wuhan) Corp	3B2-6096	http://www.3bsc.com/index/pro_info.php?id=101018
Aurora Fine Chemicals LLC	A17.996.209	http://online.aurorafinechemicals.com/info?ID=A17.996.209
BLD Pharm	BD149819	http://www.bldpharm.com/products/91-84-9.html
ChemMol	99173757	http://www.chemmol.com/chemmol/99173757.html
Clearsynth	CS-O-01879	http://www.clearsynth.com/en/CSO01879.html
DC Chemicals	DC37035	http://www.dcchemicals.com//product_show-Mepyramine.html
Finetech	FT-0628211	http://www.finetechnology-ind.com/prod/detail/pub/91-84-9.html
Hairui	HR137269	http://www.hairuichem.com/en/product/91-84-9.html
MolPort	MolPort-001-794-651	https://www.molport.com/shop/molecule-link/MolPort-001-794-651
Molcore	MC579206	https://www.molcore.com/product/91-84-9
Parchem	29372	http://www.parchem.com/chemical-supplier-distributor/Mepyramine-Maleate-019372.aspx
Sigma-Aldrich	S347108_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/s347108
Smolecule	S534993	http://www.smolecule.com/products/s534993
THE BioTek	bt-274773	https://www.thebiotek.com/product/inhibitors/bt-274773
eNovation Chemicals	Y1089293	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y1089293
iChemical	EBD4056537	http://www.ichemical.com/products/102206-59-7.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
iChemical	EBD76116	http://www.ichemical.com/products/91-84-9.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Dose-dependent inhibition of the CYP2D6 catalyzed oxidation of sparteine by mepyramine in healthy volunteers.	2001 Dec	11903961
Effects of histamine on phosphoinositide metabolism in chick cerebral cortex.	2001 Jul-Aug	11990086
Histamine H1 receptor activation stimulates mitogenesis in human astrocytoma U373 MG cells.	2001 Nov	11817705
Preclinical comparison of ebastine and other second generation H1-antihistamines.	2001 Oct	11881966
Antiallergic anti-inflammatory effects of H1-antihistamines in humans.	2002	12113215
Histochemical and biochemical studies on the secretory mechanisms of some glands of guinea-pigs treated with histamine.	2002	12056651
Topically applied aspirin decreases histamine-induced wheal and flare reactions in normal and SLS-inflamed skin, but does not decrease itch. A randomized, double-blind and placebo-controlled human study.	2002	12013195
Characterisation of the calcium responses to histamine in capsaicin-sensitive and capsaicin-insensitive sensory neurones.	2002	11958874
Antihistamine antinociception is mediated by Gi-protein activation.	2002	11927163
Impact of soil movement on carbon sequestration in agricultural ecosystems.	2002	11822721
The initial inositol 1,4,5-trisphosphate response induced by histamine is strongly amplified by Ca(2+) release from internal stores in smooth muscle.	2002 Apr	12027381
Elevated nasal mucosal G protein levels and histamine receptor affinity in a guinea pig model of nasal hyperresponsiveness.	2002 Apr	12021547
Mouse mammary epithelial cells bear histamine receptors.	2002 Apr	12013422
Insulin-induced up-regulation of histamine H1-receptors.	2002 Apr	12013418
Contractile response of horse deep dorsal penile vein to histamine.	2002 Apr	11979322
Stimulation of protein kinase B and p70 S6 kinase by the histamine H1 receptor in DDT1MF-2 smooth muscle cells.	2002 Apr	11959800
Effects of histidine, a precursor of histamine, on pentylenetetrazole-induced seizures in rats.	2002 Apr	11931695
Neuropharmacological profile of a novel potential atypical antipsychotic drug Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl)- 6H-[1]benzothieno[2,3-b][1,5] benzodiazepine maleate).	2002 Apr	11927170
GBR compounds and mepyramines as cocaine abuse therapeutics: chemometric studies on selectivity using grid independent descriptors (GRIND).	2002 Apr 11	11931612
The control effect of histamine on body temperature and respiratory function in IgE-dependent systemic anaphylaxis.	2002 Aug	12170272
Effects of histamine on the contractile and electrical activity in isolated lymphatic vessels of the guinea-pig mesentery.	2002 Aug	12163355
Functional analysis of histamine receptor subtypes involved in endothelium-mediated relaxation of the human uterine artery.	2002 Aug	12100006
Accelerated clearance of Escherichia coli in experimental peritonitis of histamine-deficient mice.	2002 Aug 15	12165523
Yawning/cortical activation induced by microinjection of histamine into the paraventricular nucleus of the rat.	2002 Aug 21	12191794
Modulation of formalin-induced behaviors and edema by local and systemic administration of dextromethorphan, memantine and ketamine.	2002 Aug 23	12206853
Biochemical characterization of desloratadine, a potent antagonist of the human histamine H(1) receptor.	2002 Aug 9	12167464
Role of mast cells in the development of pancreatitis-induced multiple organ dysfunction.	2002 Feb	11856129
Histamine-induced IL-6 and IL-8 production are differentially modulated by IFN-gamma and IL-4 in human keratinocytes.	2002 Jan	11916128
Effects of brain histamine on memory deficit induced by nucleus basalis-lesion in rats.	2002 Jan	11860740
A novel phenylaminotetralin radioligand reveals a subpopulation of histamine H(1) receptors.	2002 Jul	12065734
Antinociceptive and smooth muscle contracting activities of the methanolic extract of Cassia tora leaf.	2002 Jul	12065152
The antianaphylactic effects of Crinum glaucum aqueous extract.	2002 Jul	12065149
Suppression of spontaneous scratching in hairless rats by sedatives but not by antipruritics.	2002 Jul-Aug	12218283
Modulation of the discriminative stimulus effects of cocaine and methamphetamine by the histaminergic system.	2002 Jun	12166087
Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [(3) H]tiotidine binding.	2002 Jun	12065605
Role of Rho-associated protein kinase and histamine in lysophosphatidic acid-induced airway hyperresponsiveness in guinea pigs.	2002 Mar	11949879
Predicting the risk of Lyme disease: habitat suitability for Ixodes scapularis in the north central United States.	2002 Mar	11927027
The recovery of the neurally evoked secretory response of rat colonic mucosa after irradiation is independent of mast cells.	2002 Mar	11839088
Effects of the NMDA antagonist MK-801 on radial maze performance in histidine-deficient rats.	2002 Mar 22	12002811
Histamine excites GABAergic cells in the rat substantia nigra and ventral tegmental area in vitro.	2002 Mar 8	11852180
LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system.	2002 Nov 1	12384422
Investigation on the influx transport mechanism of pentazocine at the blood-brain barrier in rats using the carotid injection technique.	2002 Oct	12392093
Enhancement of neutrophil infiltration in histidine decarboxylase-deficient mice.	2002 Oct	12383201
Histamine h(4) and h(2) receptors control histamine-induced interleukin-16 release from human CD8(+) T cells.	2002 Oct	12235264
Effects of histamine and opioid systems on memory retention of passive avoidance learning in rats.	2002 Oct 4	12354569
Ligands for histamine H(3) receptors modulate cell proliferation and migration in rat oxyntic mucosa.	2002 Sep	12208781
Cosensitivity of vagal mucosal afferents to histamine and 5-HT in the rat jejunum.	2002 Sep	12181174
Tryptase activates the mitogen-activated protein kinase/activator protein-1 pathway in human peripheral blood eosinophils, causing cytokine production and release.	2002 Sep 1	12193739
Effects of NMDA antagonist MK-801 on radial maze performance in Zucker rats.	2002 Sep 20	12231236
Mediators of adenosine- and ovalbumen-induced bronchoconstriction of sensitized guinea-pig isolated airways.	2002 Sep 6	12223233

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Allergic Rhinitis phenylephrine-pyrilamine 25 mg-60 mg oral tablet: 1 or 2 tablets orally every 12 hours as needed. phenylephrine-pyrilamine 20 mg-16 mg oral tablet, chewable, extended release: 1 or 2 tablets orally every 12 hours as needed. phenylephrine-pyrilamine 5 mg-16 mg/5 mL oral suspension, extended release: 5 to 10 mL orally every 12 hours as needed. phenylephrine-pyrilamine 9 mg-12 mg/5 mL oral suspension, extended release: 5 to 10 mL orally every 12 hours as needed, not to exceed 20 mL in 24 hours.

Route of Administration: Oral

In Vitro Use Guide

Pretreatment with the histamine H1 receptor antagonist pyrilamine (1 uM) could reduce the beta-lactoglobulin-induced response in the in vitro guinea pig mesenteric preparation

Name

Type

Language

PYRILAMINE MALEATE

Common Name

English

PYRILAMINE MALEATE [MI]

Common Name

English

PARMAL

Brand Name

English

N-(4-METHOXYBENZYL)-N',N'-DIMETHYL-N-PYRIDIN-2-YLETHANE-1,2-DIAMINE (2Z)-BUT-2-ENEDIOATE

Systematic Name

English

ANTAMINE

Brand Name

English

2-((2-(DIMETHYLAMINO)ETHYL)(P-METHOXYBENZYL)AMINO)PYRIDINE MALEATE (1:1)

Common Name

English

MEPYRAMINE MALEATE [MART.]

Common Name

English

NEO-ANTERGAN

Brand Name

English

1,2-ETHANEDIAMINE, N-((4-METHOXYPHENYL)METHYL)-N',N'-DIMETHYL-N-2-PYRIDINYL-, (Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

ANTHISAN

Brand Name

English

PYRILAMINE MALEATE COMPONENT OF PREFRIN-A

Common Name

English

Mepyramine maleate [WHO-DD]

Common Name

English

PYRILAMINE MALEATE [VANDF]

Common Name

English

HISTALON

Brand Name

English

PYRILAMINE MALEATE [USP-RS]

Common Name

English

DORANTAMIN

Brand Name

English

THYLOGEN

Brand Name

English

STAMINE

Brand Name

English

PYRILAMINE MALEATE [ORANGE BOOK]

Common Name

English

PYRAMAL

Brand Name

English

HISTAN

Brand Name

English

PARAMINYL

Brand Name

English

MEPYRAMINE MALEATE

Common Name

English

PYRILAMINE MALEATE [USP MONOGRAPH]

Common Name

English

STANGEN

Brand Name

English

PYRILAMINE MALEATE [GREEN BOOK]

Common Name

English

ENRUMAY

Brand Name

English

MEPYRAMINE MALEATE [EP MONOGRAPH]

Common Name

English

HISTATEX

Brand Name

English

HISTAPYRAN

Brand Name

English

NSC-3604

Code

English

PREFRIN-A COMPONENT PYRILAMINE MALEATE

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 522.2063