Pergolide is a long-acting dopamine agonist approved in 1982 for the treatment of Parkinson’s Disease. It is an ergot derivative that acts on the dopamine D2 and D3, alpha2- and alpha1-adrenergic, and 5-hydroxytryptamine (5-HT) receptors. It was indicated as adjunct therapy with levodopa/carbidopa in the symptomatic treatment of parkinsonian syndrome. It was later found that pergolide increased the risk of cardiac valvulopathy. The drug was withdrawn from the US market in March 2007 and from the Canadian market in August 2007. Pergolide stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors and are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors and has been associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits agonist activity on dopamine D4, D1, and D5, 5-hydroxytryptamine (5-HT)1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, α2A-, α2B-, α2C-, α1A-, α1B-, and α1D-adrenergic receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion. Pergolide also causes transient increases in somatotropin (growth hormone) secretion and decreases in luteinizing hormone (LH) concentrations. Pergolide is not available for use by humans in the United States, but approved for veterinary use; it was used in various other countries for the treatment of various conditions including Parkinson's disease, hyperprolactinemia, and restless leg syndrome. Pergolide in Europe was indicated for Parkinson's disease only when other dopaminergic agonist treatments had failed, and treatment had to be initiated by a neurologist. The label warned against using doses of more than 5mg a day, whether alone or in combination with levodopa. However the marketing of this drug finally stopped in France in May 2011 and sales elsewhere in Europe ceased eventually.

Encainide is an antiarrhythmic drug, developed by Bristol Myers Co supplied 25 and 35 mg capsules for oral administration. Encainide is no longer used because of its frequent proarrhythmic side effects. The mechanisms of the antiarrhythmic effects of Enkaid are unknown but probably are the result of its ability to slow conduction, reduce membrane responsiveness, inhibit automaticity, and increase the ratio of the effective refractory period to action potential duration. Enkaid produces a differentially greater effect on the ischemic zone as compared with normal cells in the myocardium. This could result in the elimination of the disparity in the electrophysiologic properties between these two zones and eliminate pathways of abnormal impulse conduction, development of boundary currents and/or sites of abnormal impulse generation. The absorption of Enkaid after oral administration is nearly complete with peak plasma levels present 30 to 90 minutes after dosing. There are two major genetically determined patterns of encainide metabolism. In over 90% of patients, the drug is rapidly and extensively metabolized with an elimination half-life of 1 to 2 hours. These patients convert encainide to two active metabolites, O-demethylencainide (ODE) and 3-methoxy-O-demethylencainide (MODE), that are more active (on a per mg basis) than encainide itself. In less than 10% of patients, metabolism of encainide is slower and the estimated encainide elimination half-life is 6 to 11 hours. Slow metabolism of encainide is associated with a diminished ability to metabolize debrisoquin. Enkaid should be administered only after appropriate clinical assessment and the dosage of Enkaid must be individualized for each patient on the basis of therapeutic response and tolerance. The recommended initial dosing schedule for adults is one 25 mg Enkaid capsule t.i.d. at approximately 8-hour intervals.

Nomifensine was developed by Hoechst AG as a potent inhibitor of noradrenaline, dopamine, and 5-HT uptake displayed antidepressant activity. It was first marketed in the UK in 1977 for the treatment of depression. Between 1977 and 1982 there were reports of hemolytic anemia in association with the drug, and this suspected adverse reaction was included in the 1981 edition of the data Sheet Compendium. FDA published a notice of its determination that Merital capsules were removed from the market for safety reasons.

Zomepirac Sodium (Zomax) is a pyrrole-acetic acid structurally related to tolmetin sodium. Zomepirac is a prostaglandin synthetase inhibitor and is not an opioid, an opioid antagonist, or a salicylate. Zomepirac was approved by the Food and Drug Administration for marketing in the United States as an analgesic. It was indicated for all forms of mild to moderately severe pain, and was being promoted as a "comprehensive, non-addicting analgesic." Later Zomepirac was found to be associated with fatal and near-fatal anaphylactoid reactions. The manufacturer voluntarily removed Zomax tablets from the Canadian, US, and UK markets in March 1983.

Chlormadinone acetate (CMA) is a derivative of naturally secreted progesterone that shows high affinity and activity at the progesterone receptor. It has an anti-estrogenic effect and, in contrast to natural progesterone, shows moderate anti-androgenic properties. CMA acts by blocking androgen receptors in target organs and by reducing the activity of skin 5alpha-reductase. It suppresses gonadotropin secretion and thereby reduces ovarian and adrenal androgen production. CMA shows high contraceptive efficacy by inhibiting ovulation due to its ability to suppress or disrupt endogenous gonadotropin secretion and, by this, inhibits follicular growth and maturation. In addition, it suppresses endometrial thickness and increases the viscosity of cervical mucus. Chlormadinone acetate was withdrawn from the market in the USA, but it is still being used in Europe under the name Belara.

Phenformin is a biguanide hypoglycemic agent with actions and uses similar to those of metformin. It activates AMP-activated protein kinase (AMPK) and inhibits mTORC1 signaling. Phenformin used for the treatment of diabetes. Phenformin was removed from the U.S. market 20 years ago because of a high incidence of lactic acidosis. Risk factors for the development of lactic acidosis include renal deficiency, hepatic disease, cardiac disease, and drug interaction such as cimetidine. Phenformin exerts potential anti-neoplastic action.

Oxyphenisatin is a stimulant laxative that has been used by mouth and as an enema. Oxyphenisatin was introduced as Lavema by Winthrop in US in 1959. Oxyphenisatin was used as a cleansing enema apart from x-ray studies and prior to urinary, gastro-intestinal and cholecystography x-ray examination. Oxyphenisatin was also used for preoperative preparation of the large intestine and colon. May be mixed with barium for x-ray examination of the large intestine. Oxyphenisatin may cause jaundice. Oxyphenisatin-induced liver damage usually occurs when the drug has been taken for at least six months and usually two years. Oxyphenisatin was withdrawn in most countries in the early 1970s.

DEANOL is an inactive component of CERAVE® hydrocortisone anti-itch cream, which is used for temporarily relieve itching associated with minor skin irritations, inflammation, and rashes due to eczema, soaps, detergents, cosmetics, seborrheic dermatitis, psoriasis. DEANOL is also used as a food additive.

PECAZINE is a phenothiazine derivative that was used as an antipsychotic. It is also an allosteric inhibitor of MALT1 paracaspase activity.

Propoxyphene is a centrally acting opiate analgesic. Propoxyphene is an odorless, freely soluble in water, white crystalline powder with a bitter taste. In vitro studies demonstrated propoxyphene and the metabolite norpropoxyphene inhibit sodium channels (local anesthetic effect) with norpropoxyphene being approximately 2 fold more potent than propoxyphene and propoxyphene approximately 10 fold more potent than lidocaine. Propoxyphene and norpropoxyphene inhibit the voltage-gated potassium current carried by cardiac rapidly activating delayed rectifier (hERG) channels with approximately equal potency. It is unclear if the effects on ion channels occur within therapeutic dose range. Propoxyphene is indicated for the relief of mild to moderate pain.