MCT-125 is a fixed dose combination therapeutic in clinical development, containing lofepramine and L-phenylalanine. Lofepramine is highly specific in acting on noradrenergic neurons to block the reuptake of noradrenaline with little or no direct action of serotoninergic neurons. The synthesis of noradrenaline in noradrenergic neurons is tightly regulated by tyrosine hydroxylase acting as the key rate-limiting step controlling the flow of phenylalanine and tyrosine through to the cataecholamines. Under normal circumstances, administering either phenylalanine or tyrosine does not lead to any increase in the formation of noradrenaline due to the limited activity of tyrosine hydroxylase. MCT-125, which provides phenylalanine to drive the production of noradrenaline and lofepramine to block its reuptake, is thought to lead to the greater availability of noradrenaline in the CNS.
The pharmacology, toxicology and safety of lofepramine and L-phenylalanine separately administered, has been extensively evaluated. Lofepramine has been evaluated and approved in numerous countries in E.U. as a second generation tricyclic antidepressant; its metabolite desipramine – with overlapping pharmacological effects – has already been approved in U.S. for the same indication. L-phenylalanine is an amino acid / nutriceutical that is an excipient of numerous food and food supplement products on the market. It is expected that the pharmacological safety profile of MCT-125 will be entirely governed by its component lofepramine, while its efficacy would result from the synergy between L-phenylalanine and lofepramine.