KETOTREXATE is an antifolate developed to overcome methotrexate (MTX) resistance. However, it demonstrated such potential only in MTX-resistant sensitive L1210/FR8 leukemia cells and its clinical development was discontinued. Unlike MTX, KETOTREXATE exhibited minimal inhibition of purified dihydrofolate reductase, which implies that it does not act as a classical antifolate.

Emilium is an antiarrhythmic agent and cardiac depressant.

Piroximone is a nonglycoside, noncatecholamine inotropic agent. In animal experiments, it has been shown to increase cardiac contractility by mechanisms unrelated to any known receptor, acting mainly by inhibition of type III phosphodiesterase. Piroximone also possesses direct vasodilatory properties in the arterial and venous vascular bed. Piroximone combines well-balanced vasodilator and inotropic properties which make it very useful for the management of congestive heart failure. Piroximone had been in phase II clinical trial for the treatment of heart failure. However, this research has been discontinued.

ISOMETAMIDIUM (as a chloride salt) is widely used in tropical countries as an antiprotozoal agent to control animal trypanosomiasis. It is used principally in cattle but also in sheep, goats, buffalos, donkeys, horses, camels and dogs.

Medroxalol is a competitive antagonist at alpha1-adrenergic receptors and beta1-adrenergic receptors. Medroxalol also an agonist at beta2-adrenergic receptors. Medroxalol exerts antihypertensive and vasodilating effects. It was concluded that the principal action of medroxalol was to produce a fall in blood pressure by decreasing peripheral vascular resistance more than cardiac output.

Nitromiphene (NIT; CI 628) is a triarylethylene antiestrogen shown to be effective in treatment of experimental breast cancer. Nitromiphene is one of the earliest nonsteroidal selective estrogen receptor modulators (SERMs). It is an anti-estrogen capable to translocate the estrogen receptor to the nucleus and to induce the replenishment of the cytosol receptor. Nitromiphene inhibited the uptake of [3H]-estradiol in rat whole homogenates and isolated cell nuclei tissues and the pituitary, and inhibited estradiol-induced female sexual behavior. Nitromiphene has thus been shown to suppress the growth of chemically induced and ransplantedmammary tumors in rodents. Also, Nitromiphene was shown to have potent, prolonged antiuterotropic effects in immature rats. Nitromiphene has been shown to undergo conversion to demethyl Nitromiphene (CI628M), a phenolic metabolite which had greater affinity for estrogen receptors and greater biological potency in vitro than did Nitromiphene. However, the in vivo antiestrogenic effects of Nitromiphene and demethyl Nitromiphene were similar, possibly due to facile O-demethylation of the former compound after administration.

Phenampromide is an opioid analgesic, which is considered to be structurally similar to isomethadone. Phenampromide belongs to the ampromide family of drugs, which also include propiram and diampromide. According to the literature, (R)-phenampromide has greater analgesic potency than its (S)-enantiomer. Synthetic narcotic analgesic phenampromide is under international control according to the UN Single Convention 1961 and its amendments, Schedule I.

Guanacline was studied in the treatment of hypertension. However, information about the current use of this compound is not available.

Thyromedan is a thyroalkanoic acid derivative with hypocholesterolemic activity. In clinical trials, Thyromedan in daily doses of 8 to 32 mg caused a decrease in serum cholesterol levels. The serum total triglycerides and the α- and β-lipoprotein partition of cholesterol and triglycerides were unaffected.