Indianapolis, IN) included amino acid precursors such as L-phenylalanine, l-tyrosine, L-tryptophan, 5-hydroxytryptophane, L-glutamine, a serotonin concentrating substance chromium, an enkephalinase inhibitor D-phenylalanine, a neurotransmitter synthesis promoter vitamin B6, as well as both methionine and leucine.
The basic formula included amino acid precursors such as L-phenylalanine, l-tyrosine, L-tryptophan, 5-hydroxytryptophane, L-glutamine, a serotonin concentrating substance, chromium, an enkephalinase inhibitor D-phenylalanine, a neurotransmitter synthesis promoter vitamin B6, and as well as both methionine and leucine.
This hypothesized mechanism is supported by clinical trials utilizing amino acid neurotransmitter precursors, enkephalinase, and catechol-O-methyltransferase (COMT) enzyme inhibition, which have resulted in attenuated relapse rates in RDS probands (Blum et al.
It is thought that phenylalanine also serves to promote enkephalin activity, by acting as an enkephalinase
inhibitor potentiates substance P- and electrically induced contraction in ferret trachea.
Use of D-phenylalanine, an enkephalinase
inhibitor, in the treatment of intractable pain," Adv Pain Res Ther, 5: 305-308, 1983.
It is Pharmaleads' first molecule and the lead compound of a new class of painkillers, Dual ENKephalinase Inhibitors (DENKI).
Dual enkephalinase inhibitors (DENKI) induce natural pain relief by inhibiting the two enzymes responsible for the rapid degradation of enkephalins, the main endogenous opioids, thus increasing the level of these powerful physiological analgesics especially in pain-affected areas," according to Professors Bernard Roques and Marie-Claude Fournie-Zaluski, inventors of these molecules and co-founders of Pharmaleads.
In this regard, Blum and colleagues (1987) reversed alcohol-seeking behavior in genetically preferring C57Bl/6J mice with the chronic administration of an enkephalinase inhibitor.
Since deficits have been found in neurotransmitter functions underlying craving behavior, and since these deficits may be alleviated by facilitated dopamine release consequent to the use of opiates, nicotine, alcohol, and food, the studies mentioned above indicate enkephalinase inhibition may similarly compensate for neurotransmitter imbalance (i.
The angiotensin-converting enzyme inhibitor captopril inhibits proliferation of human ductal carcinoma cells in culture (31); in addition, angiotensin-converting enzyme and enkephalinase activities have been detected in human breast cyst fluid (32).
Angiotensin- converting enzyme and enkephalinase in human breast cyst fluid.