Salsolinol

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Salsolinol
Names
Other names
6,7-Dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
KEGG
UNII
  • InChI=1S/C10H13NO2/c1-6-8-5-10(13)9(12)4-7(8)2-3-11-6/h4-6,11-13H,2-3H2,1H3/t6-/m0/s1
    Key: IBRKLUSXDYATLG-LURJTMIESA-N
  • CC1C2=CC(=C(C=C2CCN1)O)O
Properties
C10H13NO2
Molar mass 179.219 g·mol−1
Melting point 147–149 °C (297–300 °F; 420–422 K)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Salsolinol is a chemical compound derived from dopamine which plays a role in neurotransmission and is neurotoxic.

It has been linked to dopamine-related disorders including

alcohol use disorder. It is both synthesized in the human body and ingested in several common dietary sources.[2]

Chemistry and structure

Salsolinol is a

enantiomers
: (R)-salsolinol and (S)-salsolinol. The two may have different biological effects.

The

enantioselective synthesis of the (R)-enantiomer has also been reported.[4] Salsolinol has been used as a starting material to prepare some tetrahydroisoquinoline-based prospective drugs.[5][6]

Biochemistry

Natural occurrence

Salsolinol is found in several edible plants, most prominently bananas and cocoa products as well as beer.

black cohosh, which is used in many herbal remedies, also contain salsolinol.[10]

Biosynthesis

Salsolinol is endogenously synthesized by multiple routes, although its origin in the human body remains controversial. There are two main routes for its production: one which is through a non-enantiospecific

Pictet-Spengler reaction of dopamine and acetaldehyde, and one which is mediated by the enzyme salsolinol synthase.[11]

Salsolinol synthase exclusively produces the (R)-enantiomer of salsolinol.

It has been speculated that salsolinol may also arise from salsolinol-1-carboxylic acid, which is formed by the reaction of dopamine and pyruvic acid. This transformation would occur via a proposed enzymatic pathway that has not been elucidated yet.[11]

Metabolism

Salsolinol is metabolized by an N-methyltransferase enzyme into N-methyl-(R)-salsolinol. This can then be converted by an amine oxidase into 1,2-dimethyl-6,7-dihydroxyisoquinolinium (DMDHIQ+). It can also be methylated to form its 7-methoxy and 6-methoxy versions by the enzyme catechol-O-methyltransferase (COMT).[12][11]

Salsolinol metabolism

Role in the body

Neurotoxicity and neurotransmission

Salsolinol binds to several receptors associated with dopaminergic pathways.[2][13] It may be an agonist of the μ-opioid receptor and of dopaminergic D1 and D3 receptors.[2]

Salsolinol itself also appears to be neurotoxic, the mechanism of which is not clear. Its metabolites, including N-methyl-(R)-salsolinol, also exhibit neurotoxic effects.

Prolactin

Salsolinol has been shown to be involved in the secretion of prolactin in the pituitary gland in lactating rats and lactating sheep.[14][15] Administration of a solution of salsolinol was not shown to raise prolactin levels in human women.[16]

Disease and disorders

Parkinson's disease

Salsolinol is detectable in the cerebrospinal fluid of Parkinson's disease (PD) patients and is involved in the pathogenesis of PD.[17] It is known to exercise inhibitory effects on tyrosine hydroxylase[18] and to be toxic to dopaminergic neurons.[19] A mechanism for the induction of Parkinson's by salsolinol is linked to its mediation of pyroptosis.[20]

Alcohol intake and alcohol use disorders

The connection between salsolinol and alcohol intake remains controversial. An early hypothesis was that the synthesis of salsolinol in the human body was caused by ethanol consumption, because it was being made from dopamine and acetaldehyde (a metabolite of ethanol). Several studies in the 1970s and 80s would seem to corroborate this link. However, no consistent connection between ethanol intake and salsolinol levels were conclusively established. As of the 2020s, it is understood that the primary contributor to levels of salsolinol in blood plasma is dietary intake, not acute ethanol consumption.[21] Part of the challenge in studying this is that salsolinol also is produced endogenously, and in all cases its levels are very low, making it difficult to detect and quantify with precision.[22]

Further confounding the issue, there is evidence that salsolinol may be implicated in alcohol use disorder and may play a role in increasing cravings for ethanol. (R)-Salsolinol stereospecifically induces behavioral sensitization and leads to excessive alcohol intake in rats.[23]

See also

References

  1. ^
    PMID 21270984
    . Retrieved 24 January 2024.
  2. ^
    PMID 29063289
    .
  3. S2CID 204775157
    . Retrieved 28 January 2024.
  4. doi:10.1016/j.tetasy.2012.09.009
    . Retrieved 28 January 2024.
  5. PMID 23270324
    . Retrieved 28 January 2024.
  6. PMID 10377220
    . Retrieved 28 January 2024.
  7. PMID 32560627
    .
  8. S2CID 645667
    .
  9. PMID 11087516
    . Retrieved 31 January 2024.
  10. PMID 19220011
    .
  11. ^
    PMID 29602279
    . Retrieved 28 January 2024.
  12. ISSN 0862-8408
    . Retrieved 28 January 2024.
  13. S2CID 39482201
    . Retrieved 24 January 2024.
  14. ^ Oláh, Márk; Bodnár, Ibolya; et al. (2011). "Role of salsolinol in the regulation of pituitary prolactin and peripheral dopamine release".
    PMID 29662355
    .
  15. doi:10.1016/j.smallrumres.2011.07.011
    . Retrieved 24 January 2024.
  16. PMID 3972968
    . Retrieved 24 January 2024.
  17. PMID 1598074
    . Retrieved 29 January 2024.
  18. S2CID 33317686
    . Retrieved 24 January 2024.
  19. PMID 32572814
    .
  20. S2CID 254123142
    . Retrieved 29 January 2024.
  21. PMID 19951298
    .
  22. S2CID 207089255
    . Retrieved 28 January 2024.
  23. ^ "(R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake. | PubFacts.com". www.pubfacts.com. Retrieved 2017-10-02.
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