Samidorphan was developed as a sublingually bioavailable µ-opioid receptor antagonist. This drug participated in clinical trials for the treatment of Schizophrenia, Alcohol Dependence, and Binge Eating Disorder. The oral dose pharmacokinetics, safety, and tolerability of samidorphan were evaluated in phase II double blind, placebo-controlled, randomized studies in healthy adults. In addition, the combination of samidorphan (SAM) with buprenorphine (BUP) was studied in phase III clinical trial in patients with major depressive disorder (MDM). It was shown that the long-term treatment did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low.

Buprenorphine is an opioid analgesic, used to treat opioid addiction, moderate acute pain, and moderate chronic pain. Buprenorphine is a partial agonist at the mµ-opioid receptor and an antagonist at the kappa-opioid receptor. One unusual property of buprenorphine observed in vitro studies is its very slow rate of dissociation from its receptor. This could account for its longer duration of action than morphine, the unpredictability of its reversal by opioid antagonists, and its low level of manifest physical dependence. The principal action of the therapeutic value of buprenorphine is analgesia and is thought to be due to buprenorphine binding with high affinity to opioid receptors on neurons in the brain and spinal cord. Buprenorphine produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. Buprenorphine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Buprenorphine produces peripheral vasodilation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.

L-Malic acid is a tart-tasting organic dicarboxylic acid that plays a role in many sour or tart foods. L-Malic acid is the naturally occurring form, whereas a mixture of L- and D-malic acid is produced synthetically. In humans, L-malic acid is both derived from food sources and synthesized in the body through the citric acid cycle or Krebs cycle which takes place in the mitochondria. L-Malate's importance to the production of energy in the body during both aerobic and anaerobic conditions is well established. Under aerobic conditions, the oxidation of L-malate to oxaloacetate provides reducing equivalents to the mitochondria through the malate-aspartate redox shuttle. During anaerobic conditions, where a buildup of excess of reducing equivalents inhibits glycolysis, L-malic acid's simultaneous reduction to succinate and oxidation to oxaloacetate is capable of removing the accumulating reducing equivalents. This allows L-malic acid to reverse hypoxia's inhibition of glycolysis and energy production. In studies on rats it has been found that only tissue malate is depleted following exhaustive physical activity. Notably, the administration of malic acid to rats has been shown to elevate mitochondrial malate and increase mitochondrial respiration and energy production. L-Malic acid is the source of extreme tartness in United States-produced confectionery, the so-called extreme candy. It is also used with or in place of the less sour citric acid in sour sweets. These sweets are sometimes labeled with a warning stating that excessive consumption can cause irritation of the mouth. The quantitative determination of L-malic acid is especially important in the manufacture of wine, beer, bread, fruit and vegetable products, as well as in cosmetics and pharmaceuticals. It is one of the most important fruit acids, and has the highest concentration of all acids in wine. In the wine industry, the level of L-malic acid is monitored, along with L-lactic acid, during malolactic fermentation. Malic acid is approved for use as a food additive in the EU, US and Australia and New Zealand. Malic acid, when added to food products, is denoted by E number E296.

Samidorphan was developed as a sublingually bioavailable µ-opioid receptor antagonist. This drug participated in clinical trials for the treatment of Schizophrenia, Alcohol Dependence, and Binge Eating Disorder. The oral dose pharmacokinetics, safety, and tolerability of samidorphan were evaluated in phase II double blind, placebo-controlled, randomized studies in healthy adults. In addition, the combination of samidorphan (SAM) with buprenorphine (BUP) was studied in phase III clinical trial in patients with major depressive disorder (MDM). It was shown that the long-term treatment did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low.