Monoamine Oxidase Inhibition by N-Alkyloxycarbonyl Derivatives of Ethylene Diamine

V. F. Pozdnev, L. N. Axenova, and A. E. Medvedev^*

Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, Moscow, 119832 Russia; fax: (095) 245-0857; E-mail: medvedev@ibmh.msk.su

^* To whom correspondence should be addressed.

Received January 20, 2000; Revision received February 21, 2000

---

Urethane type derivatives of ethylene diamine (EDA) were synthesized and tested as inhibitors of rat liver mitochondrial monoamine oxidase (MAO) A and B. The nature of the aromatic ring and the position of substituents in it were crucial for manifestation of the inhibitory activity. 3,4- and 2,4-Chlorobenzyloxycarbonyl-EDA derivatives were the most potent MAO A inhibitors. The inhibition of both MAO A and to a lesser extent MAO B depended on preincubation time with these inhibitors. The activity of both enzymes did not recover completely after repeated sedimentation and resuspension of inhibitor-treated mitochondria. The data suggest that these compounds exhibit properties of tight-binding reversible inhibitors of MAO A and B. The development of a new generation of MAO inhibitors causing simultaneous reversible nonselective inhibition of MAO A and B must meet one important criterion, the same type of inhibition of both the enzymes.

---

KEY WORDS: monoamine oxidase, reversible inhibitors of monoamine oxidase, urethane type derivatives of ethylene diamine

---