Physostigmine (Phy) is one of the oldest drug isolated from Calabar beans and successfully used for the treatment of glaucoma in 1864. Since then, it has been widely employed for various therapeutic purposes. Recently, it has gained prominence because of its clinical trials in the treatment of Alzheimer's disease. Physostigmine was used to treat glaucoma. It can be applied topically to the conjunctiva. Phy is also considered to be a potent prophylactic antidote for organophosphate poisoning. It is a reversible cholinesterase (ChE) inhibitor and has a short duration of action. For the last 50 years, numerous authors have shown that pretreatment with Phy would rapidly improve the incapacitating effects of organophosphate intoxication in various animal species. Phy carbamylates to a portion of ChE enzyme and thus protects the enzyme from binding with organophosphate, which are irreversible ChE inhibitors. The carbamylated ChE enzyme decarbamylates to free the enzyme for normal functioning. The rates of decarbamylation of butyrylcholinesterase (BuChE) in plasma and ChE in brain and muscle are different and are related to the half-life of Phy in these tissues. In addition to ChE inhibition, Phy has a direct action on acetylcholine (ACh) receptor ionophore complex by interacting with the ACh-gated cation channels. A cholinesterase inhibitor that is rapidly absorbed through membranes. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.

Zuretinol (QLT091001, 9-cis-retinol) is a retinoid. Retinoids (vitamin A and its analogs) are essential dietary substances that are needed by mammals for reproduction, normal embryogenesis, growth, vision, and maintaining normal cellular differentiation and the integrity of the immune system. Within cells, retinoids regulate gene transcription acting through ligand-dependent transcription factors, the retinoic acid receptors (RARs), and the retinoid X receptors (RXRs). All-trans-retinoic acid binds only to RARs with high affinity, whereas its 9-cis isomer binds with high affinity to both RARs and RXRs. The actions of all-trans- and 9-cis-retinoic acid in regulating cellular responses are distinct and not interchangeable. Zuretinol is a retinal derivative for treatment of visual disorders. It is a synthetic retinoid replacement for 11-cis-retinal. It is an investigational product under development for the treatment of retinal diseases caused by gene mutations that interfere with the availability of 11-cis-retinal. The therapeutic strategy with Zuretinol is to facilitate recovery or restoration of visual function by acting as a replacement for missing 11-cis-retinal and restoring a key biochemical component of the visual (retinoid) cycle. Novelion Therapeutics is currently developing QLT091001 for the treatment of Inherited Retinal Disease caused by retinal pigment epithelium protein 65 (“RPE65”) and lecithin:retinol acyltransferase (“LRAT”) gene mutations, which include Leber Congenital Amaurosis (“LCA”) and Retinitis Pigmentosa (“RP”). QLT091001 has received orphan drug designations for the treatment of LCA (due to inherited mutations in the LRAT and RPE65 genes) and RP (all mutations) by the U.S. Food and Drug Administration (the “FDA”), and for the treatment of LCA and RP (all mutations) by the European Medicines Agency (the “EMA”).

Octenidine dihydrochloride is a cationic surfactant, with antimicrobial activity against Gram-positive and Gram-negative bacteria. Octenidine approved as a medicinal substance in several European countries and used for skin antisepsis in combination with aliphatic alcohols, e.g. propan-1-ol and propan-2-ol, or with detergents such as antiseptic soap. Octenidine is also used for antisepsis on wounds and mucosa either as a single substance, as an approved combination of Octenidine and phenoxyethanol. Octenidine is virtually not absorbed via the skin or mucous membranes. Because Octenidine is only approved and used topically and is virtually not absorbed, no systemic effects are to be expected. Therefore, no further pharmacokinetic studies or studies on behalf of metabolism have been conducted. Octenidine is easy and safe to handle, chemically stable, not inflammable, without resistance development and low toxicity to man and the environment alike. Its popularity among therapists and wound care specialists is based on good clinical results, easy and pain-free application and local tolerance. Beside readily available combinations with phenoxyethanol, mouth rinses, and vaginal applications, semi-fluid preparations and dressings are described.

Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract. The butyric anion is easily absorbed by enteric cells and used as a main source of energy. Moreover, butyric acid is an important regulator of colonocyte proliferation and apoptosis, gastrointestinal tract motility and bacterial microflora composition in addition to its involvement in many other processes including immunoregulation and anti-inflammatory activity. Butyric acid shows a protective effect in inflammatory response secondary to inflammatory bowel diseases. A beneficial effect of butyric acid as one constituent of a multifaceted mechanism modulating gastrointestinal function has also been stressed in patients with the stoma and coexisting constipation. Butyric acid supplementation combined with the use of probiotics should be adopted as one of the basic therapeutic strategies in this patient group, preceding treatment with laxatives. Sodium butyrate in the form of enemas (combined in a mixture with A-300 silicon dioxide) may be a successful method of therapeutic management in patients with radiation proctitis. Sodium butyrate may also prevent diarrhea through an increased passive absorption of water in the colon and its effects on the gut microflora.

Clodronate (also known as clodronic acid) is a drug used to treat a high level of calcium in the blood caused by changes in the body that happen with cancer. Clodronate is approved in some countries and is sold under trade trade name bonefos for oral use. Bonefos is indicated in the management of osteolytic lesions, hypercalcemia and bone pain associated with skeletal metastases in patients with carcinoma of the breast or multiple myeloma. Bonefos is also indicated for the maintenance of clinically acceptable serum calcium levels in patients with hypercalcemia of malignancy initially treated with an intravenous bisphosphonate. Bonefos forms complexes with divalent metal ions, and therefore simultaneous administration with food, antacids and mineral supplements may impair absorption. It was suggested, that the mechanism of action of clodronate was involved osteoclast apoptosis.

Fusidic acid is a anti-bacterial agent, initially isolated from Fusidium coccineum by Godtfredsen et al (Leo Pharma) in 1960. It is discussed that fusidic acid exerts its anti-microbial effect by inhibiting bacterial elongation factor G, thus suppressing the protein synthesis. Fusidic acid is widely used in Europe under the names Fucidin H(fusidic acid / hydrocortisone acetate), Fucidin (fusidic acid / sodium fusidate) and Fucicort (fusidic acid / betamethasone valerate) for the treatment of primary/secondary skin infections and inflammatory dermatoses.

Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P) is a coenzyme, the active form of vitamin B6. Pyridoxal 5′-phosphate (PLP) is used as a cofactor for a wide range of enzymes including mitochondrial cysteine desulfurase, cystathionine γ-synthase (CGS), ornithine 4,5-aminomutase (OAM), and d-serine dehydratase. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates. PLP acts as a coenzyme in all transamination reactions, in various beta-elimination reactions, in the condensation reaction in heme synthesis.

Dichloroacetic acid, often abbreviated DCA (dichloroacetate), is an acid analog of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms. The salts and esters of dichloroacetic acid are called dichloroacetates. Salts of DCA are used as drugs since they inhibit the enzyme pyruvate dehydrogenase kinase. Early reports of its activity against brain cancer cells led patients to treat themselves with DCA, which is commercially available in non-pharmaceutical grade. A phase 1 study in 5 patients concluded that DCA was safe, but wasn't designed to establish effectiveness. DCA was approved for use in Canada in 1989 (as a topical formulation for the treatment of warts and for cauterization and removal of a wide variety of skin and tissue lesions), but was cancelled post market. DCA is a noncompetitive inhibitor of the endoplasmic reticulum enzyme HMG CoA reductase, which catalyzes the rate limiting step in cholesterol biosynthesis. DCA has been researched in adults, children, animals, and cells as a monotherapy as well as in combination with other therapies for the treatment of severe metabolic disorders including diabetes and hypercholesterolemia, lactic acidosis, certain heart conditions, and cancer. DCA has been prescribed to reduce tumour size and tumour markers, prevent angiogenesis, reduce cancer related symptoms, manage pain, and aid in palliation.

Ornithine is an amino acid produced in the urea cycle by the splitting off of urea from arginine. It is a central part of the urea cycle, which allows for the disposal of excess nitrogen. Ornithine is also a precursor of citrulline and arginine. Arginine stimulates the pituitary release of growth hormone. Burns or other injuries affect the state of arginine in tissues throughout the body. As de novo synthesis of arginine during these conditions is usually not sufficient for normal immune function, nor for normal protein synthesis, ornithine may have immunomodulatory and wound-healing activities under these conditions (by virtue of its metabolism to arginine).