EPINEPHRINE BITARTRATE

US Approved OTC

First marketed in 1901

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C9H13NO3.C4H6O6
Molecular Weight	333.2913
Optical Activity	( - )
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.CNC[C@H](O)C1=CC=C(O)C(O)=C1

InChI

InChIKey=YLXIPWWIOISBDD-NDAAPVSOSA-N

InChI=1S/C9H13NO3.C4H6O6/c1-10-5-9(13)6-2-3-7(11)8(12)4-6;5-1(3(7)8)2(6)4(9)10/h2-4,9-13H,5H2,1H3;1-2,5-6H,(H,7,8)(H,9,10)/t9-;1-,2-/m01/s1

HIDE SMILES / InChI

Molecular Formula	C4H6O6
Molecular Weight	150.0868
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C9H13NO3
Molecular Weight	183.2044
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204200s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/8401205

Epinephrine is a sympathomimetic catecholamine. It acts as a naturally occurring agonist at both alpha and beta-adrenergic receptors. Three pharmacologic types have been identified: alpha 1-, alpha 2-, and beta-adrenergic receptors. Each of these has three subtypes, characterized by both structural and functional differences. The alpha 2 and beta receptors are coupled negatively and positively, respectively, to adenylyl cyclase via Gi or Gs regulatory proteins, and the alpha 1 receptors modulate phospholipase C via the Go protein. Subtype expression is regulated at the level of the gene, the mRNA, and the protein through various transcriptional and postsynthetic mechanisms. Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor 35 Target ID: CHEMBL2331074 Sources: https://www.ncbi.nlm.nih.gov/books/NBK28138/ \| https://www.ncbi.nlm.nih.gov/pubmed/8401205	Agonist 2678
Dopamine D4 receptor 71 Target ID: CHEMBL219 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9003072	Agonist 2678		33.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anaphylaxis 46 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204200s000lbl.pdf	Primary		Approved 8429	ADRENALIN Approved Use Adrenalin® is a non-selective alpha and beta adrenergic agonist indicated for:  Emergency treatment of allergic reactions (Type 1), including anaphylaxis  Induction and maintenance of mydriasis during intraocular surgery
Miosis 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204200s000lbl.pdf	Preventing		Approved 8429	ADRENALIN Approved Use Adrenalin® is a non-selective alpha and beta adrenergic agonist indicated for:  Emergency treatment of allergic reactions (Type 1), including anaphylaxis  Induction and maintenance of mydriasis during intraocular surgery

C_max

Value	Dose	Analyte	Population
309 pg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26994624	0.3 mg single, intramuscular dose: 0.3 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	EPINEPHRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
386 pg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26994624	5 mg multiple, nasal dose: 5 mg route of administration: Nasal experiment type: MULTIPLE co-administered:	EPINEPHRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.486 ng/mL EXPERIMENT https://www.jacionline.org/article/S0091-6749(11)02197-X/pdf	0.3 mg single, intramuscular dose: 0.3 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	EPINEPHRINE unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
18.3 ng × min/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26994624	0.3 mg single, intramuscular dose: 0.3 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	EPINEPHRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.4 ng × min/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26994624	5 mg multiple, nasal dose: 5 mg route of administration: Nasal experiment type: MULTIPLE co-administered:	EPINEPHRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.724 ng × h/mL EXPERIMENT https://www.jacionline.org/article/S0091-6749(11)02197-X/pdf	0.3 mg single, intramuscular dose: 0.3 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	EPINEPHRINE unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.3 mg 1 times / day single, intramuscular Recommended Dose: 0.3 mg, 1 times / day Route: intramuscular Route: single Dose: 0.3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/201739Orig1s000MedR.pdf Page: nda/2012/201739Orig1s000MedR.pdf - p.55	healthy, 18 to 45 years old n = 66 Health Status: healthy Age Group: 18 to 45 years old Sex: M+F Population Size: 66 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/201739Orig1s000MedR.pdf Page: nda/2012/201739Orig1s000MedR.pdf - p.55	Disc. AE: Ventricular extrasystoles... AEs leading to discontinuation/dose reduction: Ventricular extrasystoles (grade 1, 1.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/201739Orig1s000MedR.pdf Page: nda/2012/201739Orig1s000MedR.pdf - p.55

AEs

AE	Significance	Dose	Population
Ventricular extrasystoles	grade 1, 1.5% Disc. AE	0.3 mg 1 times / day single, intramuscular Recommended Dose: 0.3 mg, 1 times / day Route: intramuscular Route: single Dose: 0.3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/201739Orig1s000MedR.pdf Page: nda/2012/201739Orig1s000MedR.pdf - p.55	healthy, 18 to 45 years old n = 66 Health Status: healthy Age Group: 18 to 45 years old Sex: M+F Population Size: 66 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/201739Orig1s000MedR.pdf Page: nda/2012/201739Orig1s000MedR.pdf - p.55

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 214	OCT2 355 OCT3 80	CYP2B6 547 OCT1 35

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19356039/ Page: 2.0	yes [Ki 156 uM]
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19356039/ Page: 2.0	yes [Ki 42.3 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19356039/ Page: 2.0	yes [Ki 707 uM]
CYP2B6 1001	inducer 1573 Sources: https://www.tandfonline.com/doi/abs/10.3109/00498254.2014.955831 Page: 8.0	yes
CYP3A4 1925	inducer 1573 Sources: https://www.tandfonline.com/doi/abs/10.3109/00498254.2014.955831 Page: 8.0	yes
OCT1 543	inducer 1573 Sources: https://www.tandfonline.com/doi/abs/10.3109/00498254.2014.955831 Page: 8.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes
OCT3 80	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes

PubMed

Title	Date	PubMed
Effect of intravenous citanest on adrenaline-induced ventricular fibrillation during chloroform anaesthesia.	1976	1032389
Magnesium deficiency in adult rats promotes the induction of ventricular tachycardia by the administration of epinephrine.	1998	10328182
Prolonged perioperative myocardial ischemia in a young male: due to topical intranasal cocaine?	1999 Aug	10526815
Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis.	1999 Dec	10588509
gamma2-COP, a novel imprinted gene on chromosome 7q32, defines a new imprinting cluster in the human genome.	1999 Dec	10556286
Landiolol decreases a dysrhythmogenic dose of epinephrine in dogs during halothane anesthesia.	1999 Jun	10391611
Ephedrine-induced complete atrioventricular block with ventricular asystole during rapid concomitant phenytoin infusion: a case report.	1999 Mar	10407528
[Distributive shock and it's therapy by cardio-vascular acting drugs].	1999 Oct	10570779
Spinal procaine with and without epinephrine and its relation to transient radicular irritation.	1999 Sep	10490152
Seizure suppression by systemic epinephrine is mediated by the vagus nerve.	2000 Feb	10642045
Cardiovascular studies on different classes of soft drugs.	2000 Mar	10756546
Influence of antioxidants on blood-brain barrier permeability during adrenaline-induced hypertension.	2000 Nov	11069044
Circulatory support of the sick preterm infant.	2001 Feb	11162288
Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase.	2001 Feb	11160877
Key role of the P2Y(1) receptor in tissue factor-induced thrombin-dependent acute thromboembolism: studies in P2Y(1)-knockout mice and mice treated with a P2Y(1) antagonist.	2001 Feb 6	11156884
Alterations in myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) isoenzyme-distribution in a model of left ventricular dysfunction.	2001 Jan	11163728
Influence of ABO blood groups on primary hemostasis.	2001 Jan	11161246
Viral croup.	2001 Jan	11139641
Adrenergic receptor activated ion transport in human fetal retinal pigment epithelium.	2001 Jan	11133877
Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.	2001 Jan	11120658
Neuroendocrine responses to experimentally-induced psychological stress in healthy humans.	2001 Jan	11070337
Embryonic epinephrine synthesis in the rat heart before innervation: association with pacemaking and conduction tissue development.	2001 Jan 19	11139483
The role of nitric oxide in bradycardia of rats with obstructive cholestasis.	2001 Jan 5	11137868
Mice with a deletion in the gene for CCAAT/enhancer-binding protein beta have an attenuated response to cAMP and impaired carbohydrate metabolism.	2001 Jan 5	11024029

Patents

Sample Use Guides

In Vivo Use Guide

Anaphylaxis: o Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 to 0.5 mL) intramuscularly or subcutaneously into anterolateral aspect of the thigh every 5 to 10 minutes as necessary o Children 30 kg (66 lbs) or less: 0.01 mg/kg (0.01 mL/kg), up to 0.3 mg (0.3 mL), intramuscularly or subcutaneously into anterolateral aspect of the thigh every 5 to 10 minutes as necessary (2.1) Intraocular surgery: Dilute 1 mL with 100 to 1000 mL of an ophthalmic irrigation fluid, for ophthalmic irrigation or intracameral injection

Route of Administration: Other

In Vitro Use Guide

Treatment of primary human hepatocytes with 10μM epinephrine for 24h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:10:52 GMT 2023` Edited by `admin` on `Fri Dec 15 15:10:52 GMT 2023`
Record UNII	30Q7KI53AK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

EPINEPHRINE BITARTRATE

Common Name

English

ADRENALINE (AS TARTRATE)

Common Name

English

EPINEPHRINE BITARTRATE COMPONENT OF LIGNOSPAN FORTE

Common Name

English

EPINEPHRINE BITARTRATE [JAN]

Common Name

English

EPINEPHRINE D-BITARTRATE [MI]

Common Name

English

ADRENALIN TARTRATE [WHO-IP]

Common Name

English

(-)-3,4-DIHYDROXY-.ALPHA.-((METHYLAMINO)METHYL)BENZYL ALCOHOL (+)-TARTRATE (1:1) SALT.

Common Name

English

ADRENALINE TARTRATE [EP MONOGRAPH]

Common Name

English

ADRENALINE ACID TARTRATE [MART.]

Common Name

English

MEDIHALER-EPI

Brand Name

English

Epinephrine bitartrate [WHO-DD]

Common Name

English

EPINEPHRINE BITARTRATE [ORANGE BOOK]

Common Name

English

1,2-BENZENEDIOL, 4-(1-HYDROXY-2-(METHYLAMINO)ETHYL)-, (R)-, (R-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (1:1) (SALT)

Common Name

English

EPINEPHRINE HYDROGEN TARTRATE [WHO-IP]

Common Name

English

NSC-756755

Code

English

EPINEPHRINE BITARTRATE [VANDF]

Common Name

English

ADRENALINE TARTRATE

Systematic Name

English

LIGNOSPAN FORTE COMPONENT EPINEPHRINE BITARTRATE

Common Name

English

EPINEPHRINI HYDROGENOTARTRAS [WHO-IP LATIN]

Common Name

English

BRONITIN

Brand Name

English

EPINEPHRINE TARTRATE

Common Name

English

ADRENALINE ACID TARTRATE

Common Name

English

EPINEPHRINE BITARTRATE [USP MONOGRAPH]

Common Name

English

EPINEPHRINE BITARTRATE [USP-RS]

Common Name

English

ADRENALINE BITARTATE

Common Name

English

L-EPINEPHRINE HYDROGEN TARTRATE

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 341.16