Vortioxetine is an antidepressant for the treatment of major depressive disorder. Vortioxetine’s mechanism of action is not fully understood. Vortioxetine binds with high affinity to the serotonin transporter and its antidepressant actions are believed to be secondary to enhancing serotonin in the central nervous system through inhibition of reuptake. Vortioxetine also displays binding affinities to other serotonin (5-HT) receptors, including 5-HT3, 5-HT1A, and 5-HT7. Due to multimodal neurotransmitter enhancer profile, it has been suggested that it might need lesser receptor occupancy rate for clinical trials than other selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Since vortioxetine is an agonist and antagonist of multiple serotonin receptors, potential interactions may occur with other medications that alter the serotonergic pathways. There is an increased risk of serotonin syndrome when vortioxetine is used in combination with other serotonergic agents.

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cell radiosensitizer. Later, DMF combined with three other fumaric acid esters (FAE) was licensed in Germany as oral therapy for psoriasis (trade name Fumaderm). Phase III clinical trials found that DMF (BG-12) successfully reduced relapse rate and increased time to progression of disability in multiple sclerosis (trade name Tecfidera). DMF is thought to have immunomodulatory properties without significant immunosuppression. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.

Canagliflozin (INN, trade name Invokana or Sulisent) is a drug of the gliflozin class. It was developed by Mitsubishi Tanabe Pharma and is marketed under license by Janssen, a division of Johnson & Johnson. Canagliflozin is an antidiabetic drug used to improve glycemic control in people with type 2 diabetes. Sodium-glucose co-transporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Canagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RTG), and thereby increases urinary glucose excretion. In extensive clinical trials, canagliflozin produced a consistent dose-dependent reduction in HbA1c of 0.77% to 1.16% when administered as monotherapy, combination with metformin, combination with metformin and a sulfonylurea, combination with metformin and pioglitazone, and in combination with insulin from a baselines of 7.8% to 8.1%, in combination with metformin, or in combination with metformin and a sulfonylurea. When added to metformin, canagliflozin 100 mg was shown to be non-inferior to both sitagliptin 100 mg and glimepiride in reductions on HbA1c at one year, whilst canagliflozin 300 mg successfully demonstrated statistical superiority over both sitagliptin and glimiperide in HbA1c reductions. Secondary efficacy endpoint of superior body weight reduction and blood pressure reduction (versus sitagliptin and glimiperide)) were observed as well. Canagliflozin produces beneficial effects on HDL cholesterol whilst increasing LDL cholesterol to produce no change in total cholesterol.

Vortioxetine is an antidepressant for the treatment of major depressive disorder. Vortioxetine’s mechanism of action is not fully understood. Vortioxetine binds with high affinity to the serotonin transporter and its antidepressant actions are believed to be secondary to enhancing serotonin in the central nervous system through inhibition of reuptake. Vortioxetine also displays binding affinities to other serotonin (5-HT) receptors, including 5-HT3, 5-HT1A, and 5-HT7. Due to multimodal neurotransmitter enhancer profile, it has been suggested that it might need lesser receptor occupancy rate for clinical trials than other selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Since vortioxetine is an agonist and antagonist of multiple serotonin receptors, potential interactions may occur with other medications that alter the serotonergic pathways. There is an increased risk of serotonin syndrome when vortioxetine is used in combination with other serotonergic agents.

Umeclidinium (used as a bromide salt) is a long-acting, antimuscarinic antagonist, often referred to as an anticholinergic, developed for the treatment of chronic obstructive pulmonary disease (COPD) (alone and in combination with Vilanterol - long-acting beta2-adrenergic agonist). Umeclidinium has similar affinity to the subtypes of muscarinic receptors M1 to M5 with Ki values of 0.16 nM, 0.15 nM, 0.06 nM, 0.05 nM and 0.13 nM for M1, M2, M3, M4 and M5, respectively. Umeclidinium is selective against mAChR over other unrelated receptors or channels such as κ and σ opiod receptors, Na+ channel and dopamine transporter. In the airways, it exhibits pharmacological effects through the inhibition of M3 receptor at the smooth muscle leading to bronchodilation. There is potential for an additive interaction with concomitantly used anticholinergic medicines.

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cell radiosensitizer. Later, DMF combined with three other fumaric acid esters (FAE) was licensed in Germany as oral therapy for psoriasis (trade name Fumaderm). Phase III clinical trials found that DMF (BG-12) successfully reduced relapse rate and increased time to progression of disability in multiple sclerosis (trade name Tecfidera). DMF is thought to have immunomodulatory properties without significant immunosuppression. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cell radiosensitizer. Later, DMF combined with three other fumaric acid esters (FAE) was licensed in Germany as oral therapy for psoriasis (trade name Fumaderm). Phase III clinical trials found that DMF (BG-12) successfully reduced relapse rate and increased time to progression of disability in multiple sclerosis (trade name Tecfidera). DMF is thought to have immunomodulatory properties without significant immunosuppression. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cell radiosensitizer. Later, DMF combined with three other fumaric acid esters (FAE) was licensed in Germany as oral therapy for psoriasis (trade name Fumaderm). Phase III clinical trials found that DMF (BG-12) successfully reduced relapse rate and increased time to progression of disability in multiple sclerosis (trade name Tecfidera). DMF is thought to have immunomodulatory properties without significant immunosuppression. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.

Trametinib is a reversible and specific inhibitor of mitogen-activated protein kinase kinases MEK1 and MEK2 which are involved in a RAS/RAF/MEK/ERK signaling pathway and control cell growth, survival, and differentiation. By inhibiting MEK1 and MEK2 trametinib blocks dual phosphorylation of ERK1/2 and stops cell cycling. In addition, trametinib blocks BRAF pathway in the cells with BRAF V600E mutations. Trametinib (as a single agent and in combination with dabrafenib) is approved for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations.

Vilanterol (INN, USAN) is an ultra-long-acting β2 adrenoreceptor agonist (ultra-LABA), which was approved in May 2013 in combination with fluticasone furoate for sale as Breo Ellipta by GlaxoSmithKline for the treatment of chronic obstructive pulmonary disease (COPD). Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3’,5’-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs. Vilanterol is available in following combinations: a) with inhaled corticosteroid fluticasone furoate — fluticasone furoate/vilanterol (trade names Breo Ellipta , Relvar Ellipta; b) with muscarinic antagonist umeclidinium bromide — umeclidinium bromide/vilanterol (trade name Anoro Ellipta).