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 2662
Dopamine D4 receptor 71 Target ID: CHEMBL219 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9003072	Agonist 2662		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 8360	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 8360	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 768	inhibitor 1752	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 211	OCT2 348 OCT3 79	CYP2B6 538 OCT1 21

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19356039/ Page: 2.0	yes [Ki 156 uM]
CYP3A 295	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19356039/ Page: 2.0	yes [Ki 42.3 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19356039/ Page: 2.0	yes [Ki 707 uM]
CYP2B6 985	inducer 1542 Sources: https://www.tandfonline.com/doi/abs/10.3109/00498254.2014.955831 Page: 8.0	yes
CYP3A4 1909	inducer 1542 Sources: https://www.tandfonline.com/doi/abs/10.3109/00498254.2014.955831 Page: 8.0	yes
OCT1 523	inducer 1542 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 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes
OCT3 79	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes

PubMed

Title	Date	PubMed
[Experimental anti-arrhythmic effects of a new beta-adrenergic receptor blocking agent, dl-l-(tert. butylamino)-3-[(2-propinyloxy)phenoxy]2-propanol hydrochloride (dl Kö 1400-Cl)].	1976 Jul	11153
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
Hypotensive effect of tenuifolic saponin and its mechanism.	1999 Jul	10678130
Effects of azimilide, a KV(r) and KV(s) blocker, on canine ventricular arrhythmia models.	1999 Jul 2	10440086
One hundred years of adrenaline: the discovery of autoreceptors.	1999 Jun	10454061
Investigation on SCH00013, a novel cardiotonic agent with Ca++ sensitizing action. 4th communication: influence on experimentally induced ventricular arrhythmia in dogs.	1999 May	10367104
A.E. Bennett Research Award. Developmental traumatology. Part I: Biological stress systems.	1999 May 15	10349032
[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
More Horner's than meets the eye.	2000	10886715
Reversible catecholamine-induced cardiomyopathy by subcutaneous injections of epinephrine solution in an anesthetized patient.	2000 Feb	10691253
Acute renal failure and rhabdomyolysis after inadvertent intra-arterial infusion of excessive doses of epinephrine during cardiopulmonary resuscitation.	2000 Feb 25	10726331
Aquaporin adipose, a putative glycerol channel in adipocytes.	2000 Jul 7	10777495
Antiarrhythmic and cardiohemodynamic effects of a novel Ca(2+) channel blocker, AH-1058, assessed in canine arrhythmia models.	2000 Jun 9	10856454
Cardiovascular studies on different classes of soft drugs.	2000 Mar	10756546
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
Partial agonist clonidine mediates alpha(2)-AR subtypes specific regulation of cAMP accumulation in adenylyl cyclase II transfected DDT1-MF2 cells.	2001 Feb	11160870
The effects of epidural block on the distribution of lymphocyte subsets and natural-killer cell activity in patients with and without pain.	2001 Feb	11159252
Plasma melatonin concentration before and during testosterone replacement in Klinefelter's syndrome: relation to hepatic indolamine metabolism and sympathoadrenal activity.	2001 Feb	11158039
[(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas.	2001 Feb	11158032
Oral glucose augments the counterregulatory hormone response during insulin-induced hypoglycemia in humans.	2001 Feb	11158023
Troglitazone amplifies counterregulatory responses to hypoglycemia in nondiabetic subjects.	2001 Feb	11158003
Changes in the derived central pressure waveform and pulse pressure in response to angiotensin II and noradrenaline in man.	2001 Feb 1	11158283
Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function.	2001 Feb 15	11159520
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
Early neurohormonal effects of trandolapril in patients with left ventricular dysfunction and a recent acute myocardial infarction: a double-blind, randomized, placebo-controlled multicentre study.	2001 Jan	11163738
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
Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells.	2001 Jan	11160373
Contrasting clinical properties and exercise responses in obese and lean hypertensive patients.	2001 Jan	11153733
Guanabenz, an antihypertensive centrally acting alpha2-agonist, suppresses morning elevations in aggregation of human platelets.	2001 Jan	11152378
Regulation of endothelin-1 production in cultured rat vascular smooth muscle cells.	2001 Jan	11152371
Plasma concentrations and pharmacokinetics of bupivacaine with and without adrenaline following caudal anaesthesia in infants.	2001 Jan	11152032
The PlA polymorphism of glycoprotein IIIa functions as a modifier for the effect of estrogen on platelet aggregation.	2001 Jan	11151063
Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine.	2001 Jan	11150921
Hormonal responses to exercise in chronic fatigue syndrome.	2001 Jan	11150897
Effects of high extracellular [K+] and adrenaline on force development, relaxation and membrane potential in cardiac muscle from freshwater turtle and rainbow trout.	2001 Jan	11136612
Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs.	2001 Jan	11133597
Neurotransmitter release from bovine adrenal chromaffin cells is modulated by capacitative Ca(2+)entry driven by depleted internal Ca(2+)stores.	2001 Jan	11133355
Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.	2001 Jan	11120658
Cardiovascular effects of hypercarbia in rainbow trout (Oncorhynchus mykiss): a role for externally oriented chemoreceptors.	2001 Jan	11104715
Development of glaucoma after phacoemulsification for removal of cataracts in dogs: 22 cases (1987-1997).	2001 Jan 1	11149718
Catecholamine inotropes as growth factors for Staphylococcus epidermidis and other coagulase-negative staphylococci.	2001 Jan 15	11164302
Epinephrine upregulates superoxide dismutase in human coronary artery endothelial cells.	2001 Jan 15	11163531
Hyperinsulinemia and autonomic nervous system dysfunction in obesity: effects of weight loss.	2001 Jan 30	11157715
The role of nitric oxide in bradycardia of rats with obstructive cholestasis.	2001 Jan 5	11137868
Daily cost of ophthalmic solutions for treating glaucoma in Japan.	2001 Jan-Feb	11163052
Effect of amlodipine on cardiopulmonary performance in volunteers.	2001 Jan-Feb	11153533

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 `Wed Jul 05 22:42:29 UTC 2023` Edited by `admin` on `Wed Jul 05 22:42:29 UTC 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