The isolation and naming of ergotamine by Stoll occurred in 1925 but the complete elucidation of structure was not achieved until 1951, with synthesis following some 10 years later. Current sources of ergotamine include the isolation from field ergot and fermentation broth, as well as synthesis via coupling of (+)-lysergic acid with the appropriate synthetic peptidic moiety. Ergotamine was introduced into world commerce in 1921, and is currently marketed as its water soluble tartrate salt. Ergotamine is a partial agonist at various tryptaminergic receptors (including the serotonin receptor [5-HT2]) and at various α-adrenergic receptors in blood vessels and various smooth muscles. It is likely that the major activity of ergotamine and related alkaloids is one of agonism at the 5-HT1B/1D receptors, just as with the “triptan” antimigraine compounds. FDA-labeled indications for ergotamine tartrate are in the abortion or prevention of vascular headaches, such as migraine, migraine variant, cluster headache, and histaminic cephalalgia.

Panthenol (pantothenol) is an alcohol form of the B5 vitamin pantothenic acid. It easily penetrates the skin retaining water and is a humectant, emollient and moisturizer. Panthenol mitigates signs of inflammation and stimulates epithelization. Panthenol comes in two enantiomers, D and L. Only D-panthenol (dexpanthenol) is biologically active, however both forms have moisturizing properties. Because of the ability to attract and hold moisture panthenol is used in skincare products as a humectant. It also has a role as provitamin (called pro-vitamin B5) and is used as a vitamin supplement in complex ( M.V.I. ADULT injection, Hospira Worldwide, Inc.) and alone, and as a cholinergic drug. Panthenol is a highly viscous transparent liquid at room temperature, but salts of pantothenic acid (sodium pantothenate) are powders (typically white). It is soluble in water, alcohol, propylene glycol, ether and chloroform, and slightly soluble in glycerin. Panthenol mixes readily with many different types of ingredients, making it a versatile ingredient to be used in formulas because it improves skin’s barrier function and maintains the proliferation of fibroblasts. In organisms it is quickly oxidized to pantothenate (pantothenic acid). Defficiency of Vitamin B5 results in many dermatological disorder. Due to the fact that only D-Panthenol is converted to Vitamin B5 and not L-Panthenol, the racemic mixture of D- and L- panthenol (DL-panthenol) has only half of the physiological activity of the D-Panthenol. These include stimulation of epithelisation, wound healing effect and anti-infl ammatory effect. Panthenol is FDA approved for cosmetic use and comes either in D form, or as a racemic mixture. It is also in the FDA list of over-the-counter drug products that are not generally recognized as safe and effective or are misbranded: as "Insect Bite and Sting Drug Products" and "Poison Ivy, Poison Oak, and Poison Sumac Drug Products".

Methadone, sold under the brand names Dolophine among others, is an synthetic opioid that is used as the hydrochloride to treat pain and as maintenance therapy or to help with detoxification in people with opioid dependence. Methadone hydrochloride is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine. Some data also indicate that methadone acts as an antagonist at the NMDA-receptor. The contribution of NMDA receptor antagonism to methadone’s efficacy is unknown. Most common adverse reactions are: lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. Avoid use mixed agonist/antagonist and partial agonist opioid analgesics with DOLOPHINE because they may reduce analgesic effect of DOLOPHINE or precipitate withdrawal symptoms.

Methylergometrine (other names include methylergonovine, methylergobasin, methergine, and D-lysergic acid 1-butanolamide) is a synthetic analogue of ergonovine, a psychedelic alkaloid found in ergot, and many species of morning glory. In general, the effects of all the ergot alkaloids appear to results from their actions as partial agonists or antagonists at adrenergic, dopaminergic, and tryptaminergic receptors. The spectrum of effects depends on the agent, dosage, species, tissue, and experimental or physiological conditions. All of the alkaloids of ergot significantly increase the motor activity of the uterus. After small doses contractions are increased in force or frequency, or both, but are followed by a normal degree of relaxation. As the dose is increased, contractions become more forceful and prolonged, resting tonus is markedly increased, and sustained contracture can result. Methylergometrine acts directly on the smooth muscle of the uterus and increases the tone, rate, and amplitude of rhythmic contractions through binding and the resultant antagonism of the dopamine D1 receptor. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss. Methylergometrine is used for the prevention and control of excessive bleeding following vaginal childbirth.

Dihydroergotamine (DHE) is a semisynthetic, hydrogenated ergot alkaloid, synthesized by reducing an unsaturated bond in ergotamine. Dihydroergotamine was originally envisaged as an antihypertensive agent, but it was later shown to be highly effective in treating migraine. Dihydroergotamine was first used to treat migraine in 1945 by Horton, Peters, and Blumenthal at the Mayo Clinic. In 1986, Raskin and Callaham reconfirmed the effectiveness of DHE for both intermittent and intractable migraine. The use of DHE was reviewed by Scott in 1992. In 1997, a nasal spray version was approved for use in migraine. Dihydroergotamine is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. Dihydroergotamine binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors. It also binds with high affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline α2A, α2B and α, receptors, and dopamine D2L and D3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT1D receptors. Two current theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine. One theory suggests that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of proinflammatory neuropeptide release.

Ethinyl estradiol is a synthetic derivative of the natural estrogen estradiol. It is one of two estrogens currently used in oral contraceptive pills. The other, mestranol, is converted to ethinyl estradiol before it is biologically active. Ethinyl estradiol and norethindrone are used together as an oral contraceptive agent. Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. This cascade is initiated by initially binding to the estrogen receptors. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH). Used for treatment of moderate to severe vasomotor symptoms associated with the menopause, female hypogonadism, prostatic carcinoma-palliative therapy of advanced disease, breast cancer, as an oral contraceptive, and as emergency contraceptive.

DL-Methamphetamine (also known as +/- Methamphetamin) is a central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. Methamphetamine is a mixture of two isomers. One isomer called Dextro, or D Methamphetamine, is active as a central nervous system stimulant and it is a DEA Schedule 2 controlled drug commonly called “Meth” or “Speed”. Desoxyn, a prescription drug also contains D Methamphetamine. The other isomer, Levo, or L Methamphetamine is not a DEA controlled drug. It is found in an over the counter medicine called “Vicks Inhaler” or as the prescription drug, Selegiline. (+)-methamphetamine is the more physiologically active isomer. In addition to some medications, L Methamphetamine can be produced in the illegal production of street Methamphetamine.

Pethidine, also known as meperidine and Demerol, a narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Meperidine is an opioid agonist with multiple actions qualitatively similar to those of morphine. Most common adverse reactions were lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. Pethidine has serious interactions that can be dangerous with monoamine oxidase inhibitors (e.g., furazolidone, isocarboxazid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine). Pethidine can interact with muscle relaxants, some antidepressants, benzodiazepines, and ethanol.

Deoxycholic acid is a a bile acid which emulsifies and solubilizes dietary fats in the intestine, and when injected subcutaneously, it disrupts cell membranes in adipocytes and destroys fat cells in that tissue. In April 2015, deoxycholic acid was approved by the FDA for the treatment submental fat to improve aesthetic appearance and reduce facial fullness or convexity. It is marketed under the brand name Kybella by Kythera Biopharma and is the first pharmacological agent available for submental fat reduction, allowing for a safer and less invasive alternative than surgical procedures. As a bile acid, deoxycholic acid emulsifies fat in the gut. Synthetically derived deoxycholic acid, when injected, stimulates a targeted breakdown of adipose cells by disrupting the cell membrane and causing adipocytolysis. This results in an inflammatory reaction and clearing of the adipose tissue remnants by macrophages. Deoxycholic acid's actions are reduced by albumin and tissue-associated proteins, therefore its effect is limited to protein-poor subcutaneous fat tissue. Protein-rich tissues like muscle and skin are unaffected by deoxycholic acid, contributing to its safety profile. Deoxycholic acid is a cytolytic agent. The physiologic effect of deoxycholic acid is by means of decreased cell membrane integrity. Deoxycholic acid inhibits miR-21 expression in primary rat hepatocytes in a dose-dependent manner, and increases miR-21 pro-apoptotic target programmed cell death 4 (PDCD4) and apoptosis. Deoxycholic acid decreases NF-κB activity, shown to represent an upstream mechanism leading to modulation of the miR-21/PDCD4 pathway.

Ergoalcifediol (Vitamin D2) is a fat soluble steroid hormone precursor of vitamin D. The principal biologic function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet. Cholecalciferol is synthesized within our bodies naturally, but if UV exposure is inadequate or the metabolism of cholecalciferol is abnormal, then an exogenous source is required. Vitamin D2 is converted to 25-hydroxyvitamin D (25OHD) in the liver, and then to the active form, 1,25-dihydroxyvitamin D (1,25(OH)2D), in the kidney. Once transformed, it binds to the vitamin D receptor, which leads to a variety of regulatory roles. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma. Very few foods naturally contain vitamin D. Sources that contain the vitamin include fatty fish, the liver and fat of aquatic mammals (e.g., seals, polar bears), and eggs from chickens fed vitamin D-fortified feed. As such, many countries have instituted policies to fortify certain foods with vitamin D to compensate for the potentially low exposures of skin to sunlight. Vitamin D deficiency results in inadequate mineralization of bone or compensatory skeletal demineralization and causes decreased ionized calcium concentrations in blood and a resultant increase in the production and secretion of PTH. Increase in PTH stimulates the mobilization of skeletal calcium, inhibits renal excretion of calcium, and stimulates renal excretion of phosphorus. This results in normal fasting serum calcium concentrations and low or near-normal serum phosphorus. The enhanced mobilization of skeletal calcium induced by this secondary hyperparathyroidism leads porotic bone. Ergoalcifediol is used for use in the management of hypocalcemia and its clinical manifestations in patients with hypoparathyroidism, as well as for the treatment of familial hypophosphatemia (vitamin D resistant rickets). This drug has also been used in the treatment of nutritional rickets or osteomalacia, vitamin D dependent rickets, rickets or osteomalacia secondary to long-term high dose anticonvulsant therapy, early renal osteodystrophy, osteoporosis (in conjunction with calcium), and hypophosphatemia associated with Fanconi syndrome (with treatment of acidosis). Ergocalciferol is manufactured and marketed under various names, including Deltalin (Eli Lilly and Company), Drisdol (Sanofi-Synthelabo) and Calcidol (Patrin Pharma).