OCTOPAMINE HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C8H11NO2.ClH
Molecular Weight	189.639
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.NCC(O)C1=CC=C(O)C=C1

InChI

InChIKey=PUMZXCBVHLCWQG-UHFFFAOYSA-N

InChI=1S/C8H11NO2.ClH/c9-5-8(11)6-1-3-7(10)4-2-6;/h1-4,8,10-11H,5,9H2;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22807260 | https://www.ncbi.nlm.nih.gov/pubmed/11790328 | https://www.ncbi.nlm.nih.gov/pubmed/10515667 | https://examine.com/supplements/octopamine/ | http://www.dailydoseguide.com/octopamine-dosage/

Octopamine is an organic chemical closely related to norepinephrine. In many types of invertebrates it functions as a neurotransmitter. Octopamine is known to exert adrenergic effects in mammals although specific octopamine receptors have been cloned only in invertebrates. It has been shown that octopamine can stimulate alpha(2)-adrenoceptors (ARs) in Chinese hamster ovary cells transfected with human alpha(2)-ARs. Octopamine stimulates lipolysis through beta(3)-rather than beta(1)-or beta(2)-AR activation in white adipocytes from different mammalian species. Octopamine activates only beta(3)-ARs and is devoid of alpha(2)-adrenergic agonism. Thus, octopamine could be considered as an endogenous selective beta(3)-AR agonist. In humans Octopamine is a trace amine found endogenously in the human brain where it interacts with signalling of catecholamines; it is structurally similar to synephrine and tyramine, being a metabolite of the latter (via dopamine β-hydroxylase) and substrate for the synthesis of the former (via phenethanolamine N-methyltransferase[3]) while being perhaps the closest in structure to noradrenaline. Octopamine is found in the bitter orange similar to many biogenic amines related to L-tyrosine that are used as dietary supplements, this includes synephrine and hordenine. p-Octopamine HCl (Norphen) was studied in the late 1960’s and 1970’s as a drug for the treatment of hypotensive regulatory and circulatory disorders. Octopamine was used as a nootropic. All optical isomers (enantiomers) of octopamine are on the World Anti-Doping Agency (WADA) 2014 list of substances prohibited in competition.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Beta-3 adrenergic receptor 54 Target ID: CHEMBL246 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10344530 \| https://www.ncbi.nlm.nih.gov/pubmed/24654910 \| https://examine.com/supplements/octopamine/#ref33	Agonist 2752
Beta-1 adrenergic receptor 163 Target ID: CHEMBL213 Sources: https://examine.com/supplements/octopamine/#ref32 \| https://www.ncbi.nlm.nih.gov/pubmed/37530	Agonist 2752	3.12 µM [EC50]
Dopamine transporter 183 Target ID: CHEMBL238 Sources: https://examine.com/supplements/octopamine/#ref40 \| https://www.ncbi.nlm.nih.gov/pubmed/1402923	Binding Agent 1076	220.0 µM [Kd]
Trace amine-associated receptor 1 48 Target ID: CHEMBL5857 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18524885 \| https://www.ncbi.nlm.nih.gov/pubmed/11459929 \| https://www.ncbi.nlm.nih.gov/pubmed/19725810	Agonist 2752	1.66 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypotension 29 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10344530 https://www.ncbi.nlm.nih.gov/pubmed/11790328 https://www.ncbi.nlm.nih.gov/pubmed/24654910	Primary		Approved 8583	Norphen Approved Use Hypertensive

C_max

Value	Dose	Co-administered	Analyte	Population
39.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4277715/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:		OCTOPAMINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
213 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4277715/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		OCTOPAMINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
243 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4277715/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:		OCTOPAMINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
175 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4277715/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		OCTOPAMINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
67% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4277715/			OCTOPAMINE serum	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 1079 OATP1B3 961 CYP19A1 429 CYP2C19 2057 CYP1A2 2153	P-gp 2052 OCT2 434 OCT1 393 OCT3 92

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4581#section=Biological-Test-Results Page: 1.0	inconclusive [IC50 0.1096 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4581#section=Biological-Test-Results Page: 127.0	inconclusive
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4581#section=Biological-Test-Results Page: 191.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4581#section=Biological-Test-Results Page: 181.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4581#section=Biological-Test-Results Page: 182.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4581#section=Biological-Test-Results Page: 179.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzNjc1NjUifX0=	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzNjc1NjUifX0=	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity
OCT1 393	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/36291716/	no
OCT3 92	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/36291716/	no
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4581#section=Biological-Test-Results Page: 157 \| 158	no
OCT2 434	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/36291716/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4581#section=Biological-Test-Results Page: 47.0

PubMed

Title	Date	PubMed
Distribution and action of some putative neurotransmitters in the stomatogastric nervous system of the earthworm, Eisenia fetida (Oligochaeta, Annelida).	2001 Apr	11875279
Oscillations of the transepithelial potential of moth olfactory sensilla are influenced by octopamine and serotonin.	2001 Aug	11683434
Identification of novel inhibitors of calling and in vitro [14C]acetate incorporation by pheromone glands of Plodia interpunctella.	2001 Aug	11517725
Activation and reconfiguration of fictive feeding by the octopamine-containing modulatory OC interneurons in the snail Lymnaea.	2001 Aug	11495951
Amine modulation of the transient potassium current in identified cells of the lobster stomatogastric ganglion.	2001 Dec	11731552
Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.	2001 Dec	11723224
Hormonal stimulation of proline synthesis in the fat body of the fruit beetle, Pachnoda sinuata, is calcium dependent.	2001 Dec	11719066
Inositol trisphosphate mediates the action of hypertrehalosemic hormone on fat body of the American cockroach, Periplaneta americana.	2001 Dec	11691630
Biogenic amines modulate olfactory receptor neurons firing activity in Mamestra brassicae.	2001 Jul	11473931
Effects of catecholamines on calvarial bone resorption in vitro.	2001 Jul	11465829
An in vitro method for recording the electrical activity of the isolated heart of the adult Drosophila melanogaster.	2001 Jul-Aug	11573820
Missing link in firefly bioluminescence revealed: NO regulation of photocyte respiration.	2001 Nov	11746215
Insecticidal activity of essential oils: octopaminergic sites of action.	2001 Nov	11701389
Apolipophorin-III in the greater wax moth, Galleria mellonella (Lepidoptera: Pyralidae).	2001 Nov	11673843
Regulation of the pharynx of Caenorhabditis elegans by 5-HT, octopamine, and FMRFamide-like neuropeptides.	2001 Nov 15	11745661
Categorical and prolonged potentials are evoked when brief, intermediate-intensity flashes stimulate horseshoe crab lateral eye photoreceptors during octopamine neuromodulation.	2001 Nov-Dec	11721095
Presynaptic effects of biogenic amines modulating synaptic transmission between identified sensory neurons and giant interneurons in the first instar cockroach.	2001 Oct	11763961
Ontogeny of neurohormonal regulation of the cardiovascular system in the crayfish Procambarus clarkii.	2001 Oct	11686616
Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults.	2001 Oct	11583473
Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases.	2001 Oct	11561068
Serotonergic and octopaminergic systems in the squat lobster Munida quadrispina (Anomura, Galatheidae).	2001 Oct 29	11596066
[Interaction of hormones in controlling reproductive function of Drosophila females under stressful conditions is genetically determined].	2001 Sep	11642127
Molecular and pharmacological properties of insect biogenic amine receptors: lessons from Drosophila melanogaster and Apis mellifera.	2001 Sep	11519073
Modulating the modulators: parasites, neuromodulators and host behavioral change.	2002	12563169
Modulation by 5-hydroxytryptamine of nicotinic acetylcholine responses recorded from an identified cockroach (Periplaneta americana) motoneuron.	2002 Feb	11876770
Neurotransmitters and neuropeptides in the brain of the locust.	2002 Feb 1	11810722
Comparative effects of dehydropirlindole and other compounds on rat brain monoamine oxidase type A.	2002 Jan	11853123
Fictive locomotion induced by octopamine in the earthworm.	2002 Jan	11821492
Three-dimensional common-feature hypotheses for octopamine agonist 2-(arylimino)imidazolidines.	2002 Jan	11738614
Distribution and development of dopamine- and octopamine-synthesizing neurons in the medicinal leech.	2002 Jan 7	11754166
Neurochemical fine tuning of a peripheral tissue: peptidergic and aminergic regulation of fluid secretion by Malpighian tubules in the tobacco hawkmoth M. sexta.	2002 Jul	12077163
A high-affinity octopamine transporter cloned from the central nervous system of cabbage looper Trichoplusia ni.	2002 Mar 1	11804806
Dual signalling by different octopamine receptors converges on adenylate cyclase in Sf9 cells.	2002 Mar 1	11804800
Three-dimensional common-feature hypotheses of inhibitors of calling behaviour and in vitro [14C]acetate incorporation by pheromone glands of Plodia interpunctella.	2002 Nov	12449530
Activation of octopaminergic receptors by essential oil constituents isolated from aromatic plants: possible mode of action against insect pests.	2002 Nov	12449528
Behavioural pharmacology of octopamine, tyramine and dopamine in honey bees.	2002 Nov 15	12429417
Three-dimensional common-feature hypotheses for octopamine agonist arylethanolamines.	2002 Oct	12398339
Juvenile hormone and octopamine in the regulation of division of labor in honey bee colonies.	2002 Sep	12367575
Octopamine enhances moth olfactory responses to pheromones, but not those to general odorants.	2002 Sep	12355242
Characterization of a tyramine receptor from Caenorhabditis elegans.	2002 Sep	12354282
A trace amine, tyramine, functions as a neuromodulator in Drosophila melanogaster.	2002 Sep 6	12183041
Molecular and functional characterization of an octopamine receptor from honeybee (Apis mellifera) brain.	2003 Aug	12859685
Functionally distinct dopamine and octopamine transporters in the CNS of the cabbage looper moth.	2003 Feb	12581206
Site-directed mutagenesis studies on the Drosophila octopamine/tyramine receptor.	2003 Feb	12535676
Central modulatory neurons control fuel selection in flight muscle of migratory locust.	2003 Feb 15	12598597
Positive and negative modulation of Bombyx mori adenylate cyclase by 5-phenyloxazoles: identification of octopamine and tyramine receptor agonists.	2003 Jan	12489130
Octopaminergic modulation of synaptic transmission between an identified sensory afferent and flight motoneuron in the locust.	2003 Jul 14	12761824
Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase.	2003 Jun	12777961
Elusive amines and primary headaches: historical background and prospectives.	2003 May	12811595
Metabolic flux analysis of the phenylpropanoid pathway in wound-healing potato tuber tissue using stable isotope-labeled tracer and LC-MS spectroscopy.	2003 May	12773637

Patents

Sample Use Guides

In Vivo Use Guide

When 500 mg p-octopamine was infused intravenously over 30–40 minutes into human subjects, systolic blood pressure increases of about 15 mm Hg were observed within 10 minutes. Intramuscular administration of 50 mg of a depo (slow release) form of p-octopamine into humans resulted in similar increases in systolic blood pressure.

Route of Administration: Other

In Vitro Use Guide

In isolated adipocytes from rats, the concentrations of 0.01– 0.10 nmol p-octopamine activated b-3 adrenergic receptors to lower glucose uptake into adipocytes and increase cAMP.

Name

Type

Language

OCTOPAMINE DL-FORM HYDROCHLORIDE

Preferred Name

English

OCTOPAMINE HYDROCHLORIDE

Common Name

English

Octopamine hydrochloride [WHO-DD]

Common Name

English

2-AMINO-1-(4-HYDROXYPHENYL)ETHANOL HYDROCHLORIDE

Systematic Name

English

DL-2-AMINO-1-(4-HYDROXYPHENYL)ETHANOL HYDROCHLORIDE

Common Name

English

EPIRENOR

Brand Name

English

OCTOPAMINE HYDROCHLORIDE [JAN]

Common Name

English

DL-OCTOPAMINE HYDROCHLORIDE

Common Name

English

BENZENEMETHANOL, .ALPHA.-(AMINOMETHYL)-4-HYDROXY-, HYDROCHLORIDE, (±)-

Systematic Name

English

OCTOPAMINE DL-FORM HYDROCHLORIDE [MI]

Common Name

English

(±)-P-OCTOPAMAINE HYDROCHLORIDE

Common Name

English

BENZENEMETHANOL, .ALPHA.-(AMINOMETHYL)-4-HYDROXY-, HYDROCHLORIDE

Systematic Name

English

NORFEN

Brand Name

English

NSC-108685

Code

English

BENZYL ALCOHOL, .ALPHA.-(AMINOMETHYL)-P-HYDROXY-, HYDROCHLORIDE, (±)-

Common Name

English

BENZENEMETHANOL, .ALPHA.-(AMINOMETHYL)-4-HYDROXY-, HYDROCHLORIDE (1:1)

Systematic Name

English

(±)-OCTOPAMINE HYDROCHLORIDE

Common Name

English

(±)-1-(4-HYDROXYPHENYL)-2-AMINO ETHANOL HYDROCHLORIDE

Systematic Name

English

Code System Code Type Description

PUBCHEM

20592