The alkaloid L-(-)-scopolamine [L-(-)-hyoscine], a belladonna alkaloid, competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. Scopolamine acts: i) as a competitive inhibitor at postganglionic muscarinic receptor sites of the parasympathetic nervous system, and ii) on smooth muscles that respond to acetylcholine but lack cholinergic innervation. It has been suggested that scopolamine acts in the central nervous system (CNS) by blocking cholinergic transmission from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center. Scopolamine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate, and depress motor function. Scopolamine is used for premedication in anesthesia and for the prevention of nausea and vomiting (post operative and associated with motion sickness).

Apomorphine (brand names: Apokyn, Ixense, Spontane, Uprima) is indicated for the acute, intermittent treatment of hypomobility, “off” episodes (“end-of-dose wearing off” and unpredictable “on/off” episodes) in patients with advanced Parkinson’s disease. Apomorphine has been studied as an adjunct to other medications. It is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors. The precise mechanism of action as a treatment for Parkinson’s disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.

Chlorpheniramine is an antihistamine. Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Chlorpheniramine is used for relieving symptoms of sinus congestion, sinus pressure, runny nose, watery eyes, itching of the nose and throat, and sneezing due to upper respiratory infections (eg, colds), allergies, and hay fever. In addition to being a histamine H1 receptor (HRH1) antagonist, chlorphenamine has been shown to work as a serotonin-norepinephrine reuptake inhibitor or SNRI.

Diphenhydramine is an antihistamine which is used in the combination with naproxen sodium for the relief of occasional sleeplessness when associated with minor aches and pains. Diphenhydramine has a role nighttime sleep-aid and naproxen sodium is a pain reliever. In addition, diphenhydramine used in relieving symptoms in patients with moderate-to-severe seasonal allergic rhinitis. Diphenhydramine acts as an antagonist of histamine H1 receptor. Besides, was shown potential to repurpose diphenhydramine as an anti-melanoma therapeutic agent, it induces melanoma cell apoptosis by suppressing STAT3/MCL-1 survival signaling pathway.

Ravuconazole is a triazole with antifungal properties that inhibits cytochrome P450 sterol 14a-demethylase, an enzyme involved in sterol synthesis, resulting in lysis of the fungal cell wall and fungal cell death. It was investigated for the treatment of aspergillosis, candidiasis, and onychomycosis, but these studies were discontinued. Ravuconazole is now in phase II clinical trials to investigate efficacy in preventing fungal infections in patients undergoing chemotherapy and stem cell transplantation.

Filgotinib (GLPG0634) is a highly selective JAK1 inhibitor. GLPG0634 is a promising drug candidate for the future treatment of autoimmune and inflammatory disorders. It is in phase III clinical trials (initiated mid-2016) for the treatment of rheumatoid arthritis, Crohn's disease and ulcerative colitis. Most common adverse events observed were infections, gastrointestinal disorders and nervous system disorders.

Tetrahydropalmatine is a tetrahydroprotoberberine isoquinoline alkaloid that is a primary active constituent of herbal preparations containing plant species of the genera Stephania and Corydalis. The levo isomer of THP (L-THP) appears to contribute to many of the therapeutic effects of these preparations. The pharmacological profile of L-THP, which includes antagonism of dopamine D1 and D2 receptors and actions at dopamine D3, suggests that it may have utility for treating addiction. Clinical trials where L-THP was used for the treatment of cocaine and heroin addiction have promising results. The clinical trial is planned for the treatment of schizophrenia. L-Tetrahydropalmatine is recorded in the Chinese pharmacopoeia.

Bardoxolone methyl, the C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) known as CDDO-Me or RTA 402, is one of the derivatives of synthetic triterpenoids. Bardoxolone methyl directly blocks IKKbeta activity and thereby the NF-kappaB pathway by interacting with Cys-179 in the IKKbeta activation loop. Binding of bardoxolone methyl to Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) disrupts its critical cysteine residues, leading to the release of the nuclear factor erythroid 2-related factor 2 (Nrf2), which hinders its ubiquitination and finally leads to its stabilization and nuclear translocation. In the nucleus, Nrf2 activates the transcription of phase 2 response genes, leading to a coordinated antioxidant and anti-inflammatory response. In addition, it acts as an antagonist of the peroxisome proliferator-activated receptor gamma. Through Keap1/Nrf2 and nuclear factor-κB pathways, this agent can modulate the activities of a number of important proteins that regulate inflammation, redox balance, cell proliferation and programmed cell death. This agent is generally well tolerated, but it may increase adverse cardiovascular events. Presently, it is being further tested for the treatment of patients with chronic kidney disease, cancer, and pulmonary arterial hypertension.

Daprodustat (DUVROQ) is a small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (PHD) developed by GlaxoSmithKline for the treatment of anaemia in patients with chronic kidney disease (CKD). Inhibition of PHD prevents degradation of hypoxia-inducible factor (HIF), leading to the production of erythropoietin and subsequent induction of erythropoiesis. In June, daprodustat received its first approval in Japan for the treatment of renal anaemia.

Omidenepag isopropyl, a prodrug, is hydrolyzed in the eye to the active form (Omidenepag) which functions as a selective, nonprostaglandin, prostanoid EP2 agonist, has been developed by Ube Industries and Santen Pharmaceutical as an ophthalmic solution (EYBELIS®) for the treatment of glaucoma and ocular hypertension. Omidenepag isopropyl increases the outfow of aqueous humor via both the uveoscleral outfow and the trabecular outfow pathways, resulting in potent and stable reduction in intraocular pressure (IOP). In September 2018, omidenepag isopropyl ophthalmic solution 0.002% was approved in Japan for the treatment of glaucoma and ocular hypertension. On September 22, 2022, the FDA approved Santen’s Omlonti (omidenepag isopropyl), for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.