Biology:2-Chloro-2-phenylethylamine

From HandWiki

2-Chloro-2-phenylethylamine, also known as β-chlorophenethylamine, is an irreversible inhibitor or suicidal inhibitor of the enzyme monoamine oxidase B (MAO-B),[1] irreversible inhibitor of dopamine-beta-monooxygenase,[2] a derivative of phenylethylamine in which the hydrogen atom in the β-position of the ethyl chain is replaced by a chlorine atom. This is a substituted phenylethylamine,[3][4][5] does not exhibit pronounced psychoactivity.

It is a related compound to N,N-dimethyl-2-chloro-2-phenylethylamine (DMEA), a precursor in organic synthesis.

Pharmacology

Inhibition of monoamine oxidase B

the compound It is classified as a non-medical use, selective inhibitor of monoamine oxidase B (MAO-B) that acts as a "suicide inhibitor" by covalently modifying the active site of the enzyme and completely blocking its catalytic activity.[3]

During a standard enzymatic reaction, MAO-B oxidizes the compound to 2-chloro-2-phenylacetaldehyde. The absence of significant amounts (less than 0.25 mol%) of 2-phenylacetaldehyde indicates that the reaction proceeds without the formation of a free carbanion at the C-1 atom.[3]

The mechanism of inactivation depends on the environment: under aerobic conditions, the enzyme is covalently modified by the oxidation product (2-chloro-2-phenylacetaldehyde), while under anaerobic conditions, inactivation occurs through direct alkylation by the parent compound.[1]

Inhibition of dopamine β-hydroxylase

2-Chloro-2-phenylethylamine is a suicide inhibitor of dopamine β-hydroxylase, which irreversibly inactivates them via covalent modification of the active site: in the case of MAO-B, through direct alkylation or the effect of an aldehyde product; and in the case of dopamine beta-hydrooxygenase, a bound alpha-aminoacetophenone is formed, followed by an intramolecular redox reaction to form a ketone-derived radical cation as an inhibitory substance.[5][6]

See also

References

  1. ↑ 1.0 1.1 Weyler, Walter (1987-06-01). "2-Chloro-2-phenylethylamine as a mechanistic probe and active site-directed inhibitor of monoamine oxidase from bovine liver mitochondria". Archives of Biochemistry and Biophysics 255 (2): 400–408. doi:10.1016/0003-9861(87)90408-5. ISSN 0003-9861. https://www.sciencedirect.com/science/article/pii/0003986187904085. 
  2. ↑ Bossard, M. J.; Klinman, J. P. (1990-04-05). "Use of isotope effects to characterize intermediates in mechanism-based inactivation of dopamine beta-monooxygenase by beta-chlorophenethylamine". The Journal of Biological Chemistry 265 (10): 5640–5647. ISSN 0021-9258. PMID 2318829. https://pubmed.ncbi.nlm.nih.gov/2318829. 
  3. ↑ 3.0 3.1 3.2 Weyler, W.. "2-Chloro-2-phenylethylamine as a mechanistic probe and active site-directed inhibitor of monoamine oxidase from bovine liver mitochondria". Archives of Biochemistry and Biophysics 255 (2): 400–408. doi:10.1016/0003-9861(87)90408-5. ISSN 0003-9861. PMID 3592682. https://pubmed.ncbi.nlm.nih.gov/3592682. 
  4. ↑ PubChem. "2'-Chlorophenethylamine" (in en). https://pubchem.ncbi.nlm.nih.gov/compound/99095. 
  5. ↑ 5.0 5.1 Mangold, J. B.; Klinman, J. P. (1984-06-25). "Mechanism-based inactivation of dopamine beta-monooxygenase by beta-chlorophenethylamine". The Journal of Biological Chemistry 259 (12): 7772–7779. ISSN 0021-9258. PMID 6547439. https://pubmed.ncbi.nlm.nih.gov/6547439. 
  6. ↑ Bossard, M J; Klinman, J P (1990-04-05). "Use of isotope effects to characterize intermediates in mechanism-based inactivation of dopamine beta-monooxygenase by beta-chlorophenethylamine.". Journal of Biological Chemistry 265 (10): 5640–5647. doi:10.1016/S0021-9258(19)39410-4. ISSN 0021-9258. https://www.sciencedirect.com/science/article/pii/S0021925819394104. 



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