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Details

Stereochemistry ABSOLUTE
Molecular Formula C17H25NO5
Molecular Weight 323.3841
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Dibutepinephrine

SMILES

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

InChI

InChIKey=XUROVJXCRSDXKR-ZDUSSCGKSA-N
InChI=1S/C17H25NO5/c1-10(2)16(20)22-14-7-6-12(13(19)9-18-5)8-15(14)23-17(21)11(3)4/h6-8,10-11,13,18-19H,9H2,1-5H3/t13-/m0/s1

HIDE SMILES / InChI
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.

Originator

Curator's Comment: Characterized some of the physical and biochemical properties of adrenal extract and laid the platform for purification of the active substance which was first achieved by John Abel in 1899 at Johns Hopkins University, Baltimore and independently by the Japanese scientist Jokichi Takamine in his own laboratory in New York City with the sponsorship of Parke-Davis & Co., and Thomas Aldrich (Parke-Davis & Co., Detroit, Michigan).

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Preventing
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
309 pg/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
18.3 ng × min/mL
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
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
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

Doses

DosePopulationAdverse 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: 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: Page: nda/2012/201739Orig1s000MedR.pdf - p.55
Disc. AE: Ventricular extrasystoles...
AEs leading to
discontinuation/dose reduction:
Ventricular extrasystoles (grade 1, 1.5%)
Sources: Page: nda/2012/201739Orig1s000MedR.pdf - p.55
AEs

AEs

AESignificanceDosePopulation
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: 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: Page: nda/2012/201739Orig1s000MedR.pdf - p.55
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
PubMed

PubMed

TitleDatePubMed
Biological effects of Myristica fragrans (nutmeg) extract.
1999 Jun
Landiolol decreases a dysrhythmogenic dose of epinephrine in dogs during halothane anesthesia.
1999 Jun
Adrenaline precipitated intracerebral hemorrhage.
1999 May
Investigation on SCH00013, a novel cardiotonic agent with Ca++ sensitizing action. 4th communication: influence on experimentally induced ventricular arrhythmia in dogs.
1999 May
Epinephrine-induced potentially lethal arrhythmia during arthroscopic shoulder surgery: a case report.
1999 Oct
Infiltrated lidocaine 2% with epinephrine 1:80,000 causes more postoperative pain than lidocaine 2% after oral soft tissue surgery.
1999 Spring
More Horner's than meets the eye.
2000
Influences of catecholamines on the sudden death induced in dogs by an antifungal agent, D0870.
2000 Apr
Central retinal artery occlusion after a local anesthetic with adrenaline on nasal mucosa.
2000 Dec
Low catecholamine concentrations protect adult rat ventricular myocytes against apoptosis through cAMP-dependent extracellular signal-regulated kinase activation.
2000 Dec
Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway.
2000 Feb
Effects of ubiquinone-10 on energy metabolism and lipid peroxidation in rats with myocardial ischemia.
2000 Jul
Aquaporin adipose, a putative glycerol channel in adipocytes.
2000 Jul 7
[Lactic acidosis: a complication of spinal cord injury in multiple trauma].
2000 Jun
Antiarrhythmic and cardiohemodynamic effects of a novel Ca(2+) channel blocker, AH-1058, assessed in canine arrhythmia models.
2000 Jun 9
[Acute toxic accident following lumbar plexus block with bupivacaine].
2000 May
Influence of antioxidants on blood-brain barrier permeability during adrenaline-induced hypertension.
2000 Nov
Enabling sutureless vascular bypass grafting with the exovascular sleeve anastomosis.
2000 Sep
Plasma melatonin concentration before and during testosterone replacement in Klinefelter's syndrome: relation to hepatic indolamine metabolism and sympathoadrenal activity.
2001 Feb
[(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas.
2001 Feb
Oral glucose augments the counterregulatory hormone response during insulin-induced hypoglycemia in humans.
2001 Feb
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
Alterations in myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) isoenzyme-distribution in a model of left ventricular dysfunction.
2001 Jan
Influence of ABO blood groups on primary hemostasis.
2001 Jan
Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells.
2001 Jan
Regulation of endothelin-1 production in cultured rat vascular smooth muscle cells.
2001 Jan
The PlA polymorphism of glycoprotein IIIa functions as a modifier for the effect of estrogen on platelet aggregation.
2001 Jan
Hormonal responses to exercise in chronic fatigue syndrome.
2001 Jan
Catecholamine responses to alpha-adrenergic blockade during exercise in women acutely exposed to altitude.
2001 Jan
Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs.
2001 Jan
Neurotransmitter release from bovine adrenal chromaffin cells is modulated by capacitative Ca(2+)entry driven by depleted internal Ca(2+)stores.
2001 Jan
Neonatal catecholamine levels and neurodevelopmental outcome: a cohort study.
2001 Jan
Hypoxic vasoconstriction of cyclostome systemic vessels: the antecedent of hypoxic pulmonary vasoconstriction?
2001 Jan
A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue.
2001 Jan
An accidental ringblock of the great toe?
2001 Jan
Catecholamine inotropes as growth factors for Staphylococcus epidermidis and other coagulase-negative staphylococci.
2001 Jan 15
The role of nitric oxide in bradycardia of rats with obstructive cholestasis.
2001 Jan 5
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
Patents

Patents

Sample Use Guides

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
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.
Name Type Language
Dibutepinephrine
INN  
Official Name English
PROPANOIC ACID, 2-METHYL-, 1,1'-(4-((1R)-1-HYDROXY-2-(METHYLAMINO)ETHYL)-1,2-PHENYLENE) ESTER
Systematic Name English
DIISOBUTYRYL L-EPINEPHRINE
Common Name English
4-[(1R)-1-hydroxy-2-(methylamino)ethyl]-1,2-phenylene bis(2-methylpropanoate)
Systematic Name English
DIISOBUTYRYL EPINEPHRINE
Common Name English
dibutepinephrine [INN]
Common Name English
Code System Code Type Description
CAS
2735735-23-4
Created by admin on Sat Dec 16 18:09:57 GMT 2023 , Edited by admin on Sat Dec 16 18:09:57 GMT 2023
PRIMARY
NCI_THESAURUS
C199031
Created by admin on Sat Dec 16 18:09:57 GMT 2023 , Edited by admin on Sat Dec 16 18:09:57 GMT 2023
PRIMARY
INN
12533
Created by admin on Sat Dec 16 18:09:57 GMT 2023 , Edited by admin on Sat Dec 16 18:09:57 GMT 2023
PRIMARY
PUBCHEM
163203538
Created by admin on Sat Dec 16 18:09:57 GMT 2023 , Edited by admin on Sat Dec 16 18:09:57 GMT 2023
PRIMARY
FDA UNII
3ZU4LVA3G9
Created by admin on Sat Dec 16 18:09:57 GMT 2023 , Edited by admin on Sat Dec 16 18:09:57 GMT 2023
PRIMARY