Octopamine

Octopamine

Clinical data
Other names	OCT, Norsympathol, Norsynephrine, para-Octopamine, beta-Hydroxytyramine, para-hydroxy-phenyl-ethanolamine, α-(Aminomethyl)-4 hydroxybenzenemethanol, 1-(p-Hydroxyphenyl)-2-aminoethanol
Routes of administration	Oral
ATC code	C01CA18 (WHO)
Physiological data
Source tissues	invertebrate nervous systems; trace amine in vertebrates
Target tissues	system-wide in invertebrates
Receptors	TAAR1 (mammals) OctαR, OctβR, TyrR (invertebrates), Oct-TyrR
Agonists	Formamidines (amitraz (AMZ) and chlordimeform (CDM))
Antagonists	epinastine (3-amino-9, 13b-dihydro-1H-dibenz(c,f)imidazo(1,5a)azepine hydrochloride)
Precursor	tyramine
Biosynthesis	; dopamine β-hydroxylase
Metabolism	p-hydroxymandelic acid;[1][2] N-acetyltransferases; phenylethanolamine N-methyltransferase
Legal status
Legal status	Rx / Uncontrolled / Banned by World Anti-Doping Agency
Pharmacokinetic data
Bioavailability	99.42 %
Metabolism	p-hydroxymandelic acid;[1][2] N-acetyltransferases; phenylethanolamine N-methyltransferase
Elimination half-life	15 minutes in insects. Between 76 and 175 minutes in humans
Excretion	Up to 93% of ingested octopamine is eliminated via the urinary route within 24 hours[1]
Identifiers
show IUPAC name (RS)-4-(2-amino-1-hydroxy-ethyl)phenol
CAS Number	104-14-3 Y
PubChem CID	4581
IUPHAR/BPS	2149
ChemSpider	4420 Y
UNII	14O50WS8JD
ChEBI	CHEBI:17134 N
ChEMBL	ChEMBL53929 Y
CompTox Dashboard (EPA)	DTXSID7043873
ECHA InfoCard	100.002.890
Chemical and physical data
Formula	C8H11NO2
Molar mass	153.181 g·mol−1
3D model (JSmol)	Interactive image
show SMILES OC(c1ccc(O)cc1)CN
show InChI InChI=1S/C8H11NO2/c9-5-8(11)6-1-3-7(10)4-2-6/h1-4,8,10-11H,5,9H2 Y Key:QHGUCRYDKWKLMG-UHFFFAOYSA-N Y
NY (what is this?)

Octopamine (molecular formula C₈H₁₁NO₂; also known as norsynephrine, para-octopamine and others) is an organic chemical closely related to norepinephrine, and synthesized biologically by a homologous pathway. Its name derives from the fact that it was first identified in the salivary glands of the octopus.

In many types of invertebrates octopamine is an important neurotransmitter and hormone. In protostomes — arthropods, molluscs, and several types of worms — it substitutes for norephinephrine and performs functions apparently similar to those of norepinephrine in mammals, functions that have been described as mobilizing the body and nervous system for action. In mammals octopamine is found only in trace amounts, and no biological function has been solidly established for it. It is also found naturally in numerous plants, including bitter orange.^[3][4] Octopamine has been sold under trade names such as Epirenor, Norden, and Norfen for use as a sympathomimetic drug, available by prescription.

Functions[]

Cellular effects[]

Octopamine exerts its effects by binding to and activating receptors located on the surface of cells. These receptors have mainly been studied in insects, where they can be divided into three types: alpha-adrenergic-like (OctαR), which are structurally and functionally similar to noradrenergic alpha-1 receptors in mammals; beta-adrenergic-like (OctβR), which are structurally and functionally similar to noradrenergic beta receptors in mammals; and mixed octopamine/tyramine receptors (TyrR), which are structurally and functionally similar to noradrenergic alpha-2 receptors in mammals.^[5] Receptors in the TyrR class, however, are generally more strongly activated by tyramine than by octopamine.^[5]

In vertebrates no octopamine-specific receptors have been identified. Octopamine binds weakly to receptors for norepinephrine and epinephrine, but it is not clear whether this has any functional significance. It binds more strongly to trace amine-associated receptors (TAARs), especially TAAR1.^[5]

Invertebrates[]

Octopamine was first discovered by Italian scientist Vittorio Erspamer in 1948^[6] in the salivary glands of the octopus and has since been found to act as a neurotransmitter, neurohormone and neuromodulator in invertebrates. Although Erspamer discovered its natural occurrence and named it, octopamine had actually existed for many years as a pharmaceutical product.^[7] It is widely used in energy-demanding behaviors by all insects, crustaceans (crabs, lobsters, crayfish), and spiders. Such behaviors include flying,^[8] egg-laying,^[9] and jumping.^[10][11]

Octopamine acts as the insect equivalent of norepinephrine and has been implicated in regulating aggression in invertebrates, with different effects on different species. Studies have shown that reducing the neurotransmitter octopamine and preventing coding of (an enzyme that converts tyramine to octopamine) decreases aggression in Drosophila without influencing other behaviors.^[12]

In insects, octopamine is released by a select number of neurons, but acts broadly throughout the central brain, on all sense organs, and on several non-neuronal tissues.^[13][14] In the thoracic ganglia, octopamine is primarily released by DUM (dorsal unpaired median) and VUM (ventral unpaired median) neurons, which release octopamine onto neural, muscular, and peripheral targets.^[15][16] These neurons are important for mediating energy-demanding motor behaviors, such as escape-induced jumping and flight. For example, the locust DUMeti neuron releases octopamine onto the extensor tibia muscle to increase muscle tension and increase relaxation rate. These actions promote efficient leg muscle contraction for jumping.^[13] During flight, DUM neurons are also active and release octopamine throughout the body to synchronize energy metabolism, respiration, muscle activity and flight interneuron activity.^[8] Octopamine in locusts is four times more concentrated in the axon than in the soma, and decreases the locust's myogenic rhythm.^[17]

In the honey bee and fruit fly, octopamine has a major role in learning and memory. In the firefly, octopamine release leads to light production in the lantern.^[18][19]

In lobsters, octopamine seems to direct and coordinate neurohormones to some extent in the central nervous system, and it was observed that injecting octopamine into a lobster and crayfish resulted in limb and abdomen extension.^[20]

Heberlein et al.^[21] have conducted studies of alcohol tolerance in fruit flies; they found that a mutation that caused octopamine deficiency also caused lower alcohol tolerance.^{[22][23][24][25]}

The emerald cockroach wasp stings the host for its larvae (a cockroach) in the head ganglion (brain). The venom blocks octopamine receptors^[26] and the cockroach fails to show normal escape responses, grooming itself excessively. It becomes docile and the wasp leads it to the wasp's den by pulling its antenna like a leash.^[27]

In the nematode, octopamine is found in high concentrations in adults, decreasing egg-laying and pharyngeal pumping behaviors with an antagonistic effect to serotonin.^[28]

Octopaminergic nerves in the mollusc may be present in the heart, with high concentrations in the nervous system.^[29]

In larvae of the oriental armyworm, octopamine is immunologically beneficial, increasing survival rates in high-density populations.^[30]

Vertebrates[]

In vertebrates, octopamine replaces norepinephrine in sympathetic neurons with chronic use of monoamine oxidase inhibitors. It may be responsible for the common side effect of orthostatic hypotension with these agents, though there is also evidence that it is actually mediated by increased levels of N-acetylserotonin.

One study noted that octopamine might be an important amine that influences the therapeutic effects of inhibitors such as monoamine oxidase inhibitors, especially because a large increase in octopamine levels was observed when animals were treated with this inhibitor. Octopamine was positively identified in the urine samples of mammals such as humans, rats, and rabbits treated with monoamine oxidase inhibitors. Very small amounts of octopamine were also found in certain animal tissues. It was observed that within a rabbit's body, the heart and kidney held the highest concentrations of octopamine. Octopamine was found to be 93% eluted by urine within 24 hours of being produced in the body as a byproduct of Iproniazid in rabbits.^[7]

Pharmacology[]

Octopamine has been sold under trade names such as Epirenor, Norden, and Norfen for use in medicine as a sympathomimetic drug, available by prescription. Very little information exists concerning its clinical usefulness or safety, though.^[31]

In mammals, octopamine may mobilize the release of fat from adipocytes (fat cells), which has led to its promotion on the internet as a slimming aid. However, the released fat is likely to be promptly taken up into other cells, and there is no evidence that octopamine facilitates weight loss. Octopamine may also increase blood pressure significantly when combined with other stimulants, as in some weight loss supplements.^[32]

The World Anti-Doping Agency lists octopamine as a banned substance for in competition use, as a "specified stimulant"^[33] on the 2019 Prohibited List.

Insecticides[]

The octopamine receptor is a target of insecticides, as its blockage leads to decreased cAMP levels. Essential oils can have such a neuro-insecticidal effect,^[34] and this octopamine-receptor mechanism is naturally utilized by plants with active insecticidal phytochemicals.^[35]

Biochemical mechanisms[]

Mammals[]

Octopamine is one of four primary endogenous agonists of human trace amine-associated receptor 1.^[36]

Invertebrates[]

Octopamine binds to its respective G-protein coupled receptors (GPCRs) to initiate a cell signal transduction pathway. At least three groups of octopamine GPCR have been defined. OctαR (OCTOPAMINE1 receptors) are more closely related to α-adrenergic receptors, while OctβR (OCTOPAMINE2 receptors) are more closely related to β-adrenergic receptors. The Octopamine/Tyramine receptors (including Oct-TyrR) can bind both ligands, and display agonist-specific coupling. Oct-TyrR is listed in both OCTOPAMINE and TYRAMINE RECEPTORS gene groups.^[37]

Biosynthesis[]

In humans[]

Biosynthetic pathways for catecholamines and trace amines in the human brain[38][39][40] L-Phenylalanine L-Tyrosine L-DOPA Epinephrine Phenethylamine p-Tyramine Dopamine Norepinephrine N-Methylphenethylamine N-Methyltyramine p-Octopamine Synephrine 3-Methoxytyramine AADC AADC AADC primary pathway PNMT PNMT PNMT PNMT AAAH AAAH brain CYP2D6 minor pathway COMT DBH DBH In humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid L-phenylalanine.

See also[]

• Phenethylamine
• Phenylethanolamine
• Trace amine

References[]