Chemical Properties
Off-White Solid
Usage
Acarbose is pseudo-oligosaccharide with a terminal C7-cyclitol patented in 1975 by Bayer. Acarbose is a component of the amylostatin complex produced by a species of Actinoplanes and Streptomyces. Acarbose acts as a potent inhibitor of alpha-glucosidases and saccharases. Since 1990, acarbose has been used therapeutically for the treatment of type 2 diabetes.
Usage
Acarbose is pseudo-oligosaccharide with a terminal C7-cyclitol patented in 1975 by Bayer. Acarbose is a component of the amylostatin complex produced by species of Actinoplanes and Streptomyces. Acarbose acts as a potent inhibitor of α-glucosidases and saccharases. Since 1990, acarbose has been used therapeutically for the treatment of type 2 diabetes.
Usage
alpha-glucosidase & saccharase inhibitor, antidiabetes, antihyperlipidaemia, antiobesity
Usage
antipsychotic: 5HT antagonist, dopamine antagonist, H1-antihistamine, alpha adrenergic blocker
Usage
b-glucosidase inhibitor, antidiabetic
Usage
Used as an anitdiabetic
Usage
Used as an anti-diabetic.
Uses
Acarbose is pseudo-oligosaccharide with a terminal C7-cyclitol patented in 1975 by Bayer. Acarbose is a component of the amylostatin complex produced by a species of Actinoplanes and Streptomyces. Acarbose acts as a potent inhibitor of alpha-glucosidases and saccharases. Since 1990, acarbose has been used therapeutically for the treatment of type 2 diabetes.
Uses
antipsychotic: 5HT antagonist, dopamine antagonist, H1-antihistamine, alpha adrenergic blocker
Definition
ChEBI: A tetrasaccharide derivative consisting of a dideoxy-4-{[4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl C7 cyclitol moiety [called valienol (or valienamine)] linked via nitrogen to isomaltotriose.
Brand name
Precose (Bayer).
Biological Activity
Inhibitor of intestinal α-glucosidase (IC 50 = 11 nM). Antidiabetic; inhibits the hydrolysis of complex carbohydrates.
Description
Acarbose, a complex oligosaccharide isolated from Actinoplanes, is reportedly
useful as an adjuvant therapy in diabetes. By inhibiting alpha-glucosidase,
acarbose delays carbohydrate metabolism in the gastrointestinal tract and modulates
changes in food induced blood sugar levels.
Originator
Bayer AG (Germany)
Manufacturing Process
The title compound was obtained from a cultural broth of fermenting a
microorganism of family Actinoplanaceae in particular of strain genus
Actinoplanes, according to DT-OS (German Published Specification) No.
2,347,782.
50 g of cation exchange resin (Lewatit S 1040W) in the H+ form and 30 g an
anion exchanger (Lewatit M 600) in OH form were added to 300 ml of a
culture broth with mycelium content of 25% and an inhibitor content of 50
SIU/ml in solution. The mixture was stirred at room temperature for 50
minutes. The solution, containing a sieving nozzle with 0.1 mm slits. For testing, a sample of filtered broth was centrifuged and was examined for
saccharase inhibitor in the supernatant liquor. The solution contained 2.5
SIU/ml, that is to say 5%, of starting activity. This procedure improved the
yield of the aminosugar from 20% in the procedure known from DT-OS
(German Published Specification) No. 2,347,782, to 50-60%. It has now found
that cation exchangers based on styrene, divinylbenzene and
methoxymethylmethacrylamide, oxyethyl(meth)acrylic acid amide (ester),
dimethylaminoethyl(meth)acrylic acid amide (ester) or oxypropyl(meth)acrylic
acid amide(ester) are preferred in industrial separation procedure of acarbose.
This exchanger gave a very sharp separation of the individual homologues and
impurities. And it has now found the new biosynthesis of acarbose by using of
gen engineering methods.
Therapeutic Function
Antidiabetic
World Health Organization (WHO)
Acarbose, ana-glucosidase inhibitor, is used as an adjunctive
therapy in the control of postprandial hyperglycaemia in non-insulin-dependent
diabetes mellitus. Use of two or more hypoglycaemic drugs is not recommended.
General Description
Acarbose is a naturally occurring oligosaccharide,which is obtained from the microorganism Actinoplanes utahensis. It is a white to off-white powder that is soluble in water and has a pKa of 5.1. As one mightexpect, its affinity for α-glucosidase is based on it being apolysaccharide that the enzyme attempts to hydrolyze. Thisallows acarbose to act as a competitive inhibitor, which inturn reduces the intestinal absorption of starch, dextrin, anddissacharides.
It is sold as 25-, 50-, and 100-mg tablets (Precose,generics) dosed with the first bite of each meal, up to t.i.d. Acarbose potently inhibits the glucoamylase activity of MGAM α-glucosidases and the sucrase activity of α-glucosidases, where as isomaltase activity is at most moderately inhibited at concentrations in the range of those in theintestinal lumen upon oral dosing, and trehalase and lactaseare not significantly inhibited. Some inhibition of pancreaticα-amylases may also contribute to the clinical effects.
https://www.sciencedirect.com
Biochem/physiol Actions
Modified tetrasaccharide that acts as a reversible α -glucosidase inhibitor.
Clinical Use
Based on the structure of acarbose, it should come as nosurprise that little intact acarbose reaches the systemic circulation;instead, acarbose is extensively biotransformed by the actionof microbes and digestive enzymes in the gut. Only about35% of the radioactivity in a dose of 14C-labeled acarbose administeredorally to men was excreted in the urine, appearingas several metabolites, some of which are phase II conversionproducts of 4-methylpyrogallol (O-methyl, O-sulfate, orO-glucuronide conjugates); the methylpyrogallol fragmentarises from the terminal valienamine pseudosugar. That thesebiotransformation products are mostly formed in the gut isshown by the fact that nearly 90% of an intravenously administereddose of acarbose is excreted intact in urine.
Safety Profile
Low toxicity by ingestion,subcutaneous, and intravenous routes. Human systemiceffects: liver function impaired. When heated todecomposition it emits toxic vapors of NOx.
Veterinary Drugs and Treatments
May be useful for mild reductions
in blood glucose concentrations
(250 – 350 mg/dl range) in dogs and cats with non-insulin-dependent
diabetes mellitus and as adjunctive treatment
of insulin dependent
diabetes mellitus.
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: hypoglycaemic effect possibly
enhanced and increased gastrointestinal side effects
with neomycin.
Lipid lowering agents: hypoglycaemic effect possibly
enhanced by colestyramine.
Metabolism
Oral bioavailability is 1-2%. After oral administration of
the 14C-labelled substance, on average, 35% of the total
radioactivity was excreted by the kidneys within 96 hours.
The proportion of drug excreted in the urine was 1.7% of
the administered dose. 50% of the activity was eliminated
within 96 hours in the faeces.