Octopamine

Octopamine
Ball-and-stick model of the octopamine molecule
Clinical data
Other namesOCT, 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
Physiological data
Source tissuesinvertebrate nervous systems; trace amine in vertebrates
Target tissuessystem-wide in invertebrates
ReceptorsTAAR1 (mammals)
OctαR, OctβR, TyrR (invertebrates), Oct-TyrR
AgonistsFormamidines (amitraz (AMZ) and chlordimeform (CDM))
Antagonistsepinastine (3-amino-9, 13b-dihydro-1H-dibenz(c,f)imidazo(1,5a)azepine hydrochloride)
Precursortyramine
Biosynthesistyramine β-hydroxylase; dopamine β-hydroxylase
Metabolismp-hydroxymandelic acid;[1][2] N-acetyltransferases; phenylethanolamine N-methyltransferase
Legal status
Legal status
  • Rx / Uncontrolled / Banned by World Anti-Doping Agency
Pharmacokinetic data
Bioavailability99.42 %
Metabolismp-hydroxymandelic acid;[1][3] N-acetyltransferases; phenylethanolamine N-methyltransferase
Elimination half-life15 minutes in insects. Between 76 and 175 minutes in humans
ExcretionUp to 93% of ingested octopamine is eliminated via the urinary route within 24 hours[1]
Identifiers
IUPAC name
  • (RS)-4-(2-amino-1-hydroxy-ethyl)phenol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.002.890
Edit this at Wikidata
Chemical and physical data
FormulaC8H11NO2
Molar mass153.181 g·mol−1
3D model (JSmol)
SMILES
  • OC(c1ccc(O)cc1)CN
InChI
  • InChI=1S/C8H11NO2/c9-5-8(11)6-1-3-7(10)4-2-6/h1-4,8,10-11H,5,9H2 checkY
  • Key:QHGUCRYDKWKLMG-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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.[4][5] 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.[6] Receptors in the TyrR class, however, are generally more strongly activated by tyramine than by octopamine.[6]

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.[6]

Invertebrates

Octopamine was first discovered by Italian scientist Vittorio Erspamer in 1948[7] 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.[8] It is widely used in energy-demanding behaviors by all insects, crustaceans (crabs, lobsters, crayfish), and spiders. Such behaviors include flying,[9] egg-laying,[10] and jumping.[11][12]

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 tyramine beta hydroxylase (an enzyme that converts tyramine to octopamine) decreases aggression in Drosophila without influencing other behaviors.[13]

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.[14][15] 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.[16][17] 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.[14] During flight, DUM neurons are also active and release octopamine throughout the body to synchronize energy metabolism, respiration, muscle activity and flight interneuron activity.[9] Octopamine in locusts is four times more concentrated in the axon than in the soma, and decreases the locust's myogenic rhythm.[18]

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.[19][20]

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.[21]

Heberlein et al.[22] have conducted studies of alcohol tolerance in fruit flies; they found that a mutation that caused octopamine deficiency also caused lower alcohol tolerance.[23][24][25][26]

The emerald cockroach wasp stings the host for its larvae (a cockroach) in the head ganglion (brain). The venom blocks octopamine receptors[27] 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.[28]

In the nematode, octopamine is found in high concentrations in adults, decreasing egg-laying and pharyngeal pumping behaviors with an antagonistic effect to serotonin.[29]

Octopaminergic nerves in the mollusc may be present in the heart, with high concentrations in the nervous system.[30]

In larvae of the oriental armyworm, octopamine is immunologically beneficial, increasing survival rates in high-density populations.[31]

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.[8]

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.[32]

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.[33]

The World Anti-Doping Agency lists octopamine as a banned substance for in competition use, as a "specified stimulant"[34] 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,[35] and this octopamine-receptor mechanism is naturally utilized by plants with active insecticidal phytochemicals.[36]

Biochemical mechanisms

Mammals

Octopamine is one of four primary endogenous agonists of human trace amine-associated receptor 1.[37]

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.[38]

Biosynthesis

In humans

Biosynthetic pathways for catecholamines and trace amines in the human brain[39][40][41]
Graphic of catecholamine and trace amine biosynthesis
L-Phenylalanine
L-Tyrosine
N-Methyltyramine
p-Octopamine
3-Methoxytyramine
primary
pathway
brain
CYP2D6
minor
pathway
COMT
The image above contains clickable links
In humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid L-phenylalanine.

See also

References

  1. 1 2 3 Hengstmann, J. H.; Konen, W; Konen, C; Eichelbaum, M; Dengler, H. J. (1974). "The physiological disposition of p-octopamine in man". Naunyn-Schmiedeberg's Archives of Pharmacology. 283 (1): 93–106. doi:10.1007/bf00500148. PMID 4277715. S2CID 35523412.
  2. ↑ d’Andrea, Giovanni; Nordera, Gianpietro; Pizzolato, Gilberto; Bolner, Andrea; Colavito, Davide; Flaibani, Raffaella; Leon, Alberta (2010). "Trace amine metabolism in Parkinson's disease: Low circulating levels of octopamine in early disease stages". Neuroscience Letters. 469 (3): 348–51. doi:10.1016/j.neulet.2009.12.025. PMID 20026245. S2CID 12797090.
  3. ↑ d’Andrea, Giovanni; Nordera, Gianpietro; Pizzolato, Gilberto; Bolner, Andrea; Colavito, Davide; Flaibani, Raffaella; Leon, Alberta (2010). "Trace amine metabolism in Parkinson's disease: Low circulating levels of octopamine in early disease stages". Neuroscience Letters. 469 (3): 348–51. doi:10.1016/j.neulet.2009.12.025. PMID 20026245. S2CID 12797090.
  4. ↑ Tang F, Tao L, Luo X, Ding L, Guo M, Nie L, Yao S (September 2006). "Determination of octopamine, synephrine and tyramine in Citrus herbs by ionic liquid improved 'green' chromatography". Journal of Chromatography A. 1125 (2): 182–8. doi:10.1016/j.chroma.2006.05.049. PMID 16781718.
  5. ↑ Jagiełło-Wójtowicz E (1979). "Mechanism of central action of octopamine". Polish Journal of Pharmacology and Pharmacy. 31 (5): 509–16. PMID 121158.
  6. 1 2 3 Pflüger HJ, Stevensonb PA (2005). "Evolutionary aspects of octopaminergic systems with emphasis on arthropods". Arthropod Structure & Development. 34 (3): 379–396. doi:10.1016/j.asd.2005.04.004.{{cite journal}}: CS1 maint: uses authors parameter (link)
  7. ↑ Erspamer, V. (2009). "Active Substances in the Posterior Salivary Glands of Octopoda. II. Tyramine and Octopamine (Oxyoctopamine)". Acta Pharmacologica et Toxicologica. 4 (3–4): 224–47. doi:10.1111/j.1600-0773.1948.tb03345.x.
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  30. ↑ Dougan, D. F. H.; Duffield, P. H.; Wade, D. N.; Duffield, A. M. (1 January 1981). "Occurrence and synthesis of octopamine in the heart and ganglia of the mollusc Tapes watlingi". Comparative Biochemistry and Physiology Part C: Comparative Pharmacology. 70 (2): 277–280. doi:10.1016/0306-4492(81)90064-2. ISSN 0306-4492.
  31. ↑ Kong, Hailong; Yuan, Lin; Dong, Chuanlei; Zheng, Minyuan; Jing, Wanghui; Tian, Zhen; Hou, Qiuli; Cheng, Yunxia; Zhang, Lei; Jiang, Xingfu; Luo, Lizhi (December 2020). "Immunological regulation by a β-adrenergic-like octopamine receptor gene in crowded larvae of the oriental Armyworm, Mythmina separata". Developmental and Comparative Immunology. 113: 103802. doi:10.1016/j.dci.2020.103802. ISSN 1879-0089. PMID 32712170. S2CID 220797641.
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  33. ↑ Haller CA, Benowitz NL, Jacob P (September 2005). "Hemodynamic effects of ephedra-free weight-loss supplements in humans". The American Journal of Medicine. 118 (9): 998–1003. doi:10.1016/j.amjmed.2005.02.034. PMID 16164886.
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  36. ↑ Rattan, Rameshwar Singh (1 September 2010). "Mechanism of action of insecticidal secondary metabolites of plant origin". Crop Protection. 29 (9): 913–920. doi:10.1016/j.cropro.2010.05.008. ISSN 0261-2194.
  37. ↑ Maguire JJ, Davenport AP (20 February 2018). "Trace amine receptor: TA1 receptor". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 16 July 2018.
  38. ↑ "Gene Group : OCTOPAMINE RECEPTORS", FlyBase, October 16, 2018.
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