U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Lactulose is a non-absorbable sugar used in the treatment of constipation and hepatic encephalopathy. It is a disaccharide (double-sugar) formed from one molecule each of the simple sugars (monosaccharides) fructose and galactose. Lactulose is not normally present in raw milk but is a product of heat-processed: the greater the heat, the greater amount of this substance. Lactulose is not absorbed in the small intestine nor broken down by human enzymes, thus stays in the digestive bolus through most of its course, causing retention of water through osmosis leading to softer, easier to pass stool. It has a secondary laxative effect in the colon, where it is fermented by the gut flora, producing metabolites which have osmotic powers and peristalsis-stimulating effects (such as acetate), but also methane associated with flatulence. Lactulose is metabolized in the colon by bacterial flora to short chain fatty acids including lactic acid and acetic acid. These partially dissociate, acidifying the colonic contents (increasing the H+ concentration in the gut).[14] This favors the formation of the nonabsorbable NH+4 from NH3, trapping NH3 in the colon and effectively reducing plasma NH3 concentrations. Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment. Lactulose is used for chronic idiopathic constipation, i.e. chronic constipation occurring without any identifiable cause. Lactulose may be used to counter the constipating effects of opioids, and in the symptomatic treatment of hemorrhoids as a stool softener.

Class (Stereo):
CHEMICAL (ACHIRAL)



Allopurinol is a xanthine oxidase inhibitor used to decrease high blood uric acid levels. Allopurinol is specifically used to prevent gout, prevent specific types of kidney stones, and for the high uric acid levels that can occur with chemotherapy. Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol is a structural analog of the natural purine base, hypoxanthine. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in man. Allopurinol is metabolized to the corresponding xanthine analog, oxypurinol (Allopurinol), which also is an inhibitor of xanthine oxidase. Allopurinol is taken by mouth or injected into a vein. Common side effects, when used by mouth, include itchiness and rash. Common side effects when used by injection include vomiting and kidney problems.
Amantadine hydrochloride has pharmacological actions as both an anti-Parkinson and an antiviral drug. The mechanism by which amantadine exerts its antiviral activity is not clearly understood. It appears to mainly prevent the release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. In certain cases, amantadine is also known to prevent virus assembly during virus replication. It does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine. The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. Data from earlier animal studies suggest that amantadine hydrochloride may have direct and indirect effects on dopamine neurons. More recent studies have demonstrated that amantadine is a weak, non-competitive NMDA receptor antagonist (K1 = 10µM). Although amantadine has not been shown to possess direct anticholinergic activity in animal studies, clinically, it exhibits anticholinergic-like side effects such as dry mouth, urinary retention, and constipation. Amantadine was approved by the FDA in 1966 as a prophylactic agent against Asian influenza, and eventually received approval for the treatment of influenza virus A in adults. In 1969, it was also discovered by accident to help reduce symptoms of Parkinson's disease, drug-induced extrapyramidal syndromes, and akathisia.
Furosemide, a sulfonamide-type loop diuretic structurally related to bumetanide, is used to manage hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide inhibits water reabsorption in the nephron by blocking the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. This is achieved through competitive inhibition at the chloride binding site on the cotransporter, thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium. Consequently, the lumen becomes more hypertonic while the interstitium becomes less hypertonic, which in turn diminishes the osmotic gradient for water reabsorption throughout the nephron. Because the thick ascending limb is responsible for 25% of sodium reabsorption in the nephron, furosemide is a very potent diuretic. Furosemide is sold under the brand name Lasix among others.
Acetylcholine is the neurotransmitter at neuromuscular junctions, at synapses in the ganglia of the visceral motor system, and at a variety of sites within the central nervous system. Whereas a great deal is known about the function of cholinergic transmission at the neuromuscular junction and at ganglionic synapses, the actions of acetylcholine in the central nervous system are not as well understood. Cholinergic system is an important system and a branch of the autonomic nervous system which plays an important role in memory, digestion, control of heart beat, blood pressure, movement and many other functions. Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity, and coordinates firing of groups of neurons. Miochol®-E (acetylcholine chloride intraocular solution) is used to obtain miosis of the iris in seconds after delivery of the lens in cataract surgery, in penetrating keratoplasty, iridectomy and other anterior segment surgery where rapid miosis may be required.
Status:
First approved in 1966

Class (Stereo):
CHEMICAL (ABSOLUTE)


Conditions:

Etynodiol (used in a form of diacetate) is a steroid that was used as a contraceptive drug. Etynodiol diacetate and etynodiol are rapidly metabolized to an active metabolite, norethisterone, which binds to progesterone receptor and modulates its activity.
Status:
US Previously Marketed
First approved in 1966

Class (Stereo):
CHEMICAL (ACHIRAL)



Sulfametoxydiazine (INN) or sulfamethoxydiazine (USAN: sulfameter) is a long-acting sulfonamide antibacterial, shows bacteriostatic effects against Gram positive and Gram negative bacteria in vivo. It is used as a leprostatic agent and in the treatment of urinary tract infections. Orally active. Sulfonamides block the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase. Sulfonamides are competitive inhibitors of bacterial para-aminobenzoic acid (PABA), which is required for bacterial synthesis of folic acid. Sulfameter is a dihydrofolate reductase (DHFR) inhibitor. Mode of resistance is via the alteration of dihydropteroate synthase or alternative pathway for folic acid synthesis.
Status:
US Previously Marketed
Source:
Solhar by Person-Covey
(1966)
Source URL:
First approved in 1966
Source:
Solhar by Person-Covey
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)

Conditions:

Dioxybenzone (benzophenone-8) is an organic compound used in sunscreen to block UVB and short-wave UVA rays. It is a derivative of benzophenone. It is insoluble in water, which lends to the ‘waterproof’ claims that sunscreens make. It’s approved for use in the US at a concentration of 3%.
Status:
US Previously Marketed
First approved in 1966

Class (Stereo):
CHEMICAL (ACHIRAL)

Targets:


Pipobroman (trade names Vercite, Vercyte) is an anti-cancer drug that probably acts as an alkylating agent. It is marketed by Abbott Laboratories. Pipobroman (PB) has well documented clinical activity in polycythemia vera (PV) and essential thrombocythemia (ET). The mechanism of action is uncertain but pipobroman is thought to alkylate DNA leading to disruption of DNA synthesis and eventual cell death
Status:
US Previously Marketed
Source:
Oracon by Mead Johnson
(1966)
Source URL:
First approved in 1966
Source:
Oracon by Mead Johnson
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)

Conditions:

Dimethisterone (brand name Secrosteron) is an orally active progestational agent. It was developed by the British pharmaceutical company British Drug Houses and was first reported in the literature in 1959 with introduction for medical use as Secrosteron. Relative to ethisterone, it is 12 times as potent orally as a progestogen in animals (Clauberg test). It has an oral LD50 in mice of 7.65 g/kg, no apparent anabolic, androgenic properties and no significant effect on sodium, potassium or water excretion in saline loaded rats. Dimethisterone was introduced in the United States as an oral contraceptive for birth control in combination with ethinylestradiol under the brand name Oracon (25 mg dimethisterone, 100 ug ethinylestradiol) and was produced by Mead Johnson & Company (Evansville, Indiana) in 1974. This preparation was eventually found to be associated with a substantially increased risk of endometrial cancer in women, and is now no longer marketed.