n-(2-aminoethyl)-4-chlorobenzamide-hydrochloride and brofaromine

In this paper an overview of the present state of monoamine oxidase inhibitors (MAOIs) is presented. The irreversible inhibitors are firstly considered. They have been divided into four chemical types: substituted hydrazine, cyclopropylamine, propargylamine and allylamine derivatives. Moreover, a tetrahydropyridine derivative (MPTP), recently described as an irreversible inhibitor of MAO-B, has been included among the irreversible MAOIs. The reversible inhibitors such as tetrahydro-beta-carbolines and salsolinol, phenylalkylamines: amphetamine, amiflamine and 2,3-dichloro-alpha-methyl-benzylamine. Among the short acting or reversible inhibitors the 4-(2-benzofuranyl) piperidine series and the morpholinoethylamino derivatives are discussed. Finally the oxazolidinone series is presented separately, as in this series reversible or irreversible inhibitors of the A or B form of MAO have been obtained.

Topics: Animals; Benzamides; Humans; Hydrazines; Isoquinolines; Monoamine Oxidase Inhibitors; Oxazoles; Oxazolidinones; Parkinson Disease; Phenethylamines; Piperidines; Selegiline; Structure-Activity Relationship

The inhibition of monoamine oxidase (MAO) in rat liver and brain by the short-acting MAO-A inhibitors moclobemide (Ro 11-1163 = p-chloro-N-[2-morpholinoethyl]benzamide) and brofaremine and by the short-acting MAO-B inhibitors Ro 16-6491 (N-[2-aminoethyl]-p-chloro-benzamide) and almoxatone, administered p.o. at roughly equieffective doses 2 h before decapitation, was investigated for its reversibility under various in vitro conditions. MAO A activity in liver homogenates, inhibited by moclobemide (300 mumol/kg) to approx. 15% of control, time dependently recovered during 0.5 to 2 h of incubation at 37 degrees C, irrespective of whether the homogenates were prepared and incubated in distilled water or Krebs-Ringer buffer (KRB). Dialysis of such homogenates for 4 h in distilled water at 37 degrees C (but not at 13 degrees C) led to a complete return of the MAO activity. In liver homogenates from rats pretreated with brofaremine (30 mumol/kg), dialysis for 4 h at 37 degrees C against distilled water caused only little recovery of the MAO activity. Likewise, MAO-B inhibited by Ro 16-6491 (30 mumol/kg) to approx. 4% of control returned to almost control activity after 4 h of dialysis at 37 degrees C, while inhibition induced by almoxatone (30 mumol/kg) was little or not reversed at all. In brain homogenates prepared in, and dialysed against, distilled water or KRB at 37 degrees C (but not at 13 degrees C), MAO-A inhibited by moclobemide (100-300 mumol/kg) to approx. 15% of control, partially (KRB) or almost completely (dist. water) returned to control activity after 4 h of dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Benzamides; Brain; Brain Chemistry; Dialysis; In Vitro Techniques; Liver; Male; Moclobemide; Monoamine Oxidase Inhibitors; Piperidines; Rats; Tyramine