As we know, cyclodextrins are composed of α-D-glucopyranose units. Among pharmaceuticals there are several other carbohydrate type drugs. In this series of posts aiming education we will take a closer look to those molecules that are carbohydrate- type active pharmaceutical ingredients (APIs) (including sugar alcohols, imino- and aminosugars), from monosaccharides to polysaccharides. But we won’t talk about:
- excipients (e.g. maltodextrins, carboxymethyl cellulose),
- commercially available mono- and disaccharides (e.g. glucose, saccharose, lactose),
- carbohydrate part of glycosides (e.g. digitoxose),
- sweeteners (e.g. sucralose),
- nucleoside type drugs (e.g. lamivudine, acyclovir)
First let’s see a few monosaccharides with active pharmacological effects, starting from smaller molecules.
Pentaerythritol tetranitrate (PETN, 1) can be used for the acute treatment of angina pectoris. This molecule is a derivative of erythritol and works by releasing the signaling gas nitric oxide in the body. However, the pure substance is highly explosive.
From this class we can mention another two molecules, which are derivatives of the D-glucose: isosorbide-mono and -dinitrate (2). All of them are taken orally.
Topiramate (3) is a sugar sulfamate, first synthesized in the late 70s by Maryanoff1 in an antidiabetic project. However, this molecule doesn’t have any antidiabetic effect, it is an antiepileptic drug (also used in migraine prophylaxis) with complex mechanisms of action, including voltage-dependent sodium channels, GABA receptors, and glutamate receptors. It is an O-substituted β-D-fructopyranose. The 2,3- and 4,5-hydroxyl groups form acetonides, and the primary one is part of the sulfamate ester. It is taken orally.
Zanamivir (4) (Relenza®) and laninamivir (5) (Inavir® only in JP)- are antiviral drugs, used for prevention of influenza (caused by influenza A and B viruses). Both are neuraminidase inhibitors. By blocking the viral enzyme, these molecules prevent virus reproduction by budding from the host cell. There are other neuraminidase inhibitors (e.g. oseltamivir (Tamiflu® or peramivir (Rapivab®), but only zanamivir and laninamivir are carbohydrate type drugs. These molecules are the derivatives of N-acetylneuraminic acid (6), a nonose (a monosaccharide with nine carbons). The route of administration is inhalation for both of them (zanamivir by oral, laninamivir by nasal).
Last but not least let’s see a ‘precious’ little molecule –auranofin (7) (Ridaura®). It is an organogold monosaccharide -a derivative of D-glucose, used to treat rheumatoid arthritis, but also has anti-infective effects. It is taken orally.
In Part 2 we take a brief detour to the (mono)iminosugars and rare diseases.
1 Maryanoff, B; Phenotypic Assessment and the Discovery of Topiramate, ACS Med Chem Let, 2016, 7(7):662-665
2 Wisniewski, M; Lukasik-Glebocka M, and Anand JS: Acute Topiramate Overdose–Clinical Manifestations. Clin Toxicol (Phila), 2009, 47(4):317-20