An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. Papaverine is a vasodilating agent. Papaverine is used for the treating certain conditions that are accompanied by smooth muscle spasms (eg, blood vessel, urinary, gallbladder, or intestinal spasm). Papaverine is a nonxanthine phosphodiesterase inhibitor for the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias. The main actions of Papaverine are exerted on cardiac and smooth muscle. Like qathidine, Papaverine acts directly on the heart muscle to depress conduction and prolong the refractory period. Papaverine relaxes various smooth muscles. This relaxation may be prominent if spasm exists. The muscle cell is not paralyzed by Papaverine and still responds to drugs and other stimuli causing contraction. The antispasmodic effect is a direct one, and unrelated to muscle innervation. Papaverine is practically devoid of effects on the central nervous system. Papaverine relaxes the smooth musculature of the larger blood vessels, especially coronary, systemic peripheral, and pulmonary arteries. Papaverine is a potent, specific inhibitor of PDE10A. Papaverine for treatment of erectile dysfunction (ED) is excluded from coverage.

As an aid in the prevention of coccidiosis caused by Eimeria adenoeides, E.gallopavonis, and E.meleagrimitis; for the prevention of bacterial infections caused by Pasteurella multocida (fowl cholera); for the treatment of skin and soft tissue infections. Ormetoprim potentiates the activity of sulfadimethoxine. The in vitro antibacterial spectrum and activity of the 2 compounds are very similar. Sulfonamides competitively inhibit bacterial synthesis of folic acid (pteroylglutamic acid) from paraaminobenzoic acid. Conditions reported following use of sulfonamides or potentiated sulfonamides include polyarthritis, urticaria, facial swelling, fever, hemolytic anemia, polydypsia, polyuria, hepatitis, vomiting, anorexia, diarrhea, and neurologic disorders. In rare instances, neurologic signs including behavioral changes, ataxia, seizures, aggression, and hyperexcitability have been reported. Keratitis sicca, possibly due to prolonged use of sulfonamides, has been reported.

Calcium-D-glucarate (also known as CALCIUM SACCHARATE) is the calcium salt of D-glucaric acid, a substance produced naturally in small amounts by mammals, including humans. Oral supplementation of calcium-D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme produced by colonic microflora and involved in Phase II liver detoxification. Elevated beta-glucuronidase activity is associated with an increased risk for various cancers, particularly hormone-dependent cancers such as breast, prostate, and colon cancers. Other potential clinical applications of oral calcium-D-glucarate include regulation of estrogen metabolism and as a lipid-lowering. In addition, by reducing the beta-glucuronidase viability and activity of intestinal bacteria, salts of D-glucaric acid have been shown to enhance enterohepatic circulation and reduce steady state levels of cholesterol synthesis, resulting in decreased serum lipid levels.

Enoximone is an inhibitor of PDE3, which is used for the treatment of congestive heart failure. Also enoximone was shown to inhibit PDH in cardiac myocytes. The inhibition was shown to occur secondary to stimulating fatty acid oxidation

Pentifylline is an active vasodilating substance which does not affect blood sugar levels. Pentifylline inhibits the soluble and the particulate cyclic AMP phosphodiesterases from bovine platelets and rat brain ATPase. The inhibition of ATPase by pentifylline was not influenced by the change in Na /K ratio. Pentifylline in combination with Nicotinic acid indicated for the treatment of Cerebral circulatory disorders and Circulatory disorders of the eye. Pentifylline is well tolerated but it is recommended that blood pressure be monitored and if there is a severe drop in blood pressure, a drip infusion of plasma expander be administered. Coagulation states should also be closely watched.

Voglibose is an alpha glucosidase inhibitor, which was initially marketed in Japan as an improving agent for postprandial hyperglycemia in diabetes mellitus. Later on the drug was approved for the prevention of type 2 diabetes. The drug is available in Asia under the name Basen.

Iproclozide [1-(p-chlorophenoxyacetyl)-2-isopropylhydrazine] is a non-selective monoamine oxidase inhibitor. It has been used in the treatment of depressive states. Iproclozide was studied in the treatment of hypertension and angina pectoris. It may induce fatal hepatitis.

Olprinone (INN) is a cardiotonic agent, is used for treatment acute heart failure. It has been marketed in Japan since 1996. The main mechanism of action of olprinone hydrochloride hydrate is selective inhibition of PDE III specific to cAMP. It is considered that this action causes an increase in intracellular cAMP levels and peak Ca2+ levels, thereby increasing myocardial contractility.

Batebulast (NCO-650) is an anti-allergic drug. It significantly inhibited both the initial and secondary increases in cAMP stimulated by antigen, anti-IgE and concanavalin A (Con A) in rat peritoneal mast cells. It strongly inhibited the incorporation of the 3H-methyl moiety into phospholipid by antigen, anti-IgE and Con A during histamine release. Batebulast significantly inhibited the compound 48/80-induced bronchoconstriction in dogs. Batebulast had no effect on the bronchoconstriction induced by inhalation of acetylcholine, suggesting that NCO-650 appears to have no anti-cholinergic effect and thus no effect on the vagal reflex that occurred during the asthmatic responses. NCO-650 may be useful for the treatment of bronchial asthma as an orally active drug. Batebulast has been in phase II clinical trials for the treatment of asthma in Japan. However, this research has been discontinued.