Salsolinol
From Wikipedia, the free encyclopedia
 | |
| Names | |
|---|---|
| Other names
6,7-Dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline | |
| Identifiers | |
3D model (JSmol) |
|
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| KEGG | |
PubChem CID |
|
| UNII | |
| |
| |
| 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 tetrahydroisoquinoline derived from dopamine which plays a role in neurotransmission and is a dopaminergic neurotoxin.
It has been linked to dopamine-related disorders including Parkinson's disease and alcohol use disorder. It is both synthesized in the human body and ingested in several common dietary sources.[2]
Salsolinol is a catechol isoquinoline which is a yellow solid at room temperature.[1] Salsolinol, as a chiral molecule, comes in two enantiomers: (R)-salsolinol and (S)-salsolinol. The two may have different biological effects.
The racemate can be synthesized via a Pictet-Spengler reaction.[3] A chemoenzymatic, 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.[7][8][9] Other plants, including 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]
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]