Toloxatone

Reversible Inhibitors of Monoamine Oxidase. Selective MAO-A inhibitors, which aie leveisible (so-called RIMAs), have also been developed, theiefoie substantially leduciag the potential foi food and dmg iateiactions. Indeed, the tyiamine-potentiating effects of these dmgs is much reduced compared with the irreversible MAO inhibitors. The RIMAs represent effective and safer alternatives to the older MAO inhibitors. The only marketed RIMAs ate toloxatone [29218-27-7] and moclobemide (55). The latter is used widely as an effective, weU-tolerated antidepressant. 

CjHioOj 105-58-8) see Ambuside Bisoprolol Fenspiride Flurbiprofen Furazolidone Ketoprofen Mephenytoin Nifuratel Pheno barbital Pranoprofen Protizinic acid Temafloxacin Toloxatone Tybamate Zolmitriptan... 

Reversible ( RIMA ) Befloxaton Brofaromine Moclobemide Pirlindole Toloxatone ... 

Figure 7.1, Structural formulae of some monoamine oxidase inhibitors (moclobemide, pirlindole and toloxatone) and alpha2 adrenoceptor antagonists [S-...

I. J. Koenig, F.X. Jarreau, A reversible monoamine oxidase inhibitor, toloxatone structural and electronic properties, Eur. J. Med. Chem. 27 (1992) 939-948. 

In terms of the new MAO inhibitors that may become available in the future, it is possible that some new RIMAs may be approved as antidepressants. Moclobemide, available in many countries, is unlikely, for commercial reasons, to become available in the United States. Another promising RIMA, brofaramine, is also unlikely to be developed for any country. However, befloxatone is progressing in clinical trials, and other RIMAs are also potential drug development candidates, including RS-8359, cimoxatone, and toloxatone. 

Like moclobemide, toloxatone, a selective and reversible inhibitor of monoamine oxidase type A, is thought to be relatively safe in combination with sympathomimetics (SEDA-18, 16). However, sweating, tachycardia, and headache have been reported when terbutaline was added to toloxatone and phenylephrine (SEDA-18, 16). In healthy volunteers, doses up to 600 mg/day did not produce hypertensive reactions on challenge with oral tyramine (SEDA-17, 17). Two fatal cases of fulminant hepatitis have been reported (SEDA-16, 7). 

Interactions with toloxatone are similar to those with moclobemide (1). 

Iproniazid (MarsUid, Iprozid, Ipronid, Rivivol, PropUniazida) Iproclozide Toloxatone... 

Some of the major drugs in the category of MAOs include phenelzine, 50, moclobemide, 51, toloxatone, 52, and others. Tranylcypromine (trans-phenyl-cyclopropylamine), 53, was one of the first MAO inactivators approved for clinical use [6]. 

All available monoamine oxidase (MAO) inhibitors (excepting moclobemide, toloxatone, brofaromine, and selegiline) act via a suicide mechanism, by causing long-lasting, irreversible, competitive inhibition of... 

Then in the 1980s there was a reappraisal of the benefit-to-harm balance of the MAO inhibitors. This spawned both a search for safer and more selective or rapidly reversible enzyme inhibitors (including moclobemide, toloxatone, and brofaromine), as well as a review and retrial of the older compounds. 

Sweating, tachycardia, and headache have been reported when terbutaline was added to toloxatone (SEDA-18,16). 

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