clozapine and rasagiline

Multitargeting is a valuable concept in drug design for the development of effective drugs for the treatment of multifactorial diseases. This concept has most frequently been realized by incorporating two or more pharmacophores into a single hybrid molecule. Many such hybrids, due to the increased molecular size, exhibit unfavorable physicochemical properties leading to adverse effects and/or an inappropriate ADME (absorption, distribution, metabolism, and excretion) profile. To avoid this limitation and achieve additional therapeutic benefits, here we describe a novel multitargeting strategy based on the synergistic effects of a parent drug and its active metabolite(s). The concept of metabolism-activated multitargeting (MAMUT) is illustrated using a number of examples.

Topics: Amine Oxidase (Copper-Containing); Anti-Inflammatory Agents; Antipsychotic Agents; Cell Adhesion Molecules; Central Nervous System Diseases; Clozapine; Drug Design; Drug Synergism; Humans; Indans; Ligands; Monoamine Oxidase; Pharmaceutical Preparations; Receptor, Muscarinic M1