α-Methyldopamine

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Alpha-Methyldopamine
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α-Methyldopamine
Identifiers
  • 4-(2-aminopropyl)benzene-1,2-diol
JSmol)
  • Oc1ccc(cc1O)CC(N)C
  • InChI=1S/C9H13NO2/c1-6(10)4-7-2-3-8(11)9(12)5-7/h2-3,5-6,11-12H,4,10H2,1H3 checkY
  • Key:KSRGADMGIRTXAF-UHFFFAOYSA-N checkY
  (verify)

α-Methyldopamine (α-Me-DA), also known as 3,4-dihydroxyamphetamine (3,4-DHA or HHA), is a

neurotoxic when directly injected into the brain's ventricles
.

Interest lies in the fact that

5-HIAA (its major metabolite in the body) in vivo following administration. A common theory follows that a metabolite in the periphery must be responsible, and several have been cited as responsible. Although alpha-methyldopamine is widely cited as the source of this neurotoxicity in a number of lay sources, McCann, et al. (1991), demonstrated that the major metabolites alpha-methyldopamine (α-Me-DA or HHA) and 3-O-methyl-α-methyldopamine (3-O-Me-α-MeDA or HMA) did not produce neurotoxicity.[1]

It was first demonstrated, in 1978, by Conway, et al. and possibly others that, while alpha-methyldopamine caused acute decreases in the levels of neuronal dopamine, in some areas of the brain in excess of 75%, levels returned to baseline within 12 hours, indicating that alpha-methyldopamine could not be responsible for the toxic effects observed.[2]

However, the story complicates as alpha-methyldopamine readily oxidizes to the o-quinone and reacts with endogenous antioxidants in the body, such as glutathione (GSH). It was demonstrated by Miller, et al. (1997), that 5-(glutathion-S-yl)-alpha-methyldopamine and 5-(N-acetylcystein-S-yl)-alpha-methyldopamine produced similar effects to the parent compound, but did not induce neurotoxicity when injected intracerebroventricularly. However the derivative metabolite 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine (injected at ≈1.5x the usual per-kg MDMA dose) did in fact induce neurotoxicity, providing initial evidence that this metabolite may be the source of neuronal toxicity following the administration of MDA and MDMA, and the subsequent reduction in 5-HT (Serotonin) axons.[3]

See also

  • α-Methylnorepinephrine
  • α-Methyltyramine

References

  1. S2CID 2574803
    .
  2. PMID 729639
    .
  3. PMID 9128836
    .
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