ATC Group: R05D Cough suppressants, excl. combinations with expectorants

Butamirate (or brospamin) is a cough suppressant. It binds to the cough center in the medulla oblongata, more specifically the dextromethorphan-binding site in guinea pig brain with high affinity.

Clofedanol is a centrally-acting cough suppressant, although the mechanism of action is not known. Clofedanol suppresses the cough reflex by a direct effect on the cough center in the medulla of the brain. It also has local anesthetic and antihistamine properties, and may have anticholinergic effects at high doses.

Cloperastine is an antitussive and antihistamine that is marketed as a cough suppressant. The precise mechanism of action of cloperastine is not fully clear, but several different biological activities have been identified for the drug, of which include: ligand of the gamma1 receptor (Ki = 20 nM) (likely an agonist), GIRK channel blocker (described as “potent”), antihistamine (Ki = 3.8 nM for the H1 receptor), and anticholinergic. Cloperastine possesses dual activity. It also acts as a mild bronchorelaxant and has antihistaminic activity, without acting on the central nervous system or the respiratory center.

Codeine is a centrally acting weak analgesic. Codeine exerts its effect through μ opioid receptors, although codeine has low affinity for these receptors, and its analgesic effect is due to its conversion to morphine. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain. The anti-tussive activity of codeine is probably due to its depressant effect on the medullary cough centre in the brain.

Dextromethorphan is a non-opioid antitussive drug. The major metabolite of dextromethorphan, dextrorphan, binds with high affinity to σ-receptors to produce its antitussive activity without exhibiting the classic opiate effects that occur from binding into μ- and δ-receptors. In larger than therapeutic doses, dextrorphan is also an antagonist of N-methyl-D-aspartate (NMDA) receptors.

Ethylmorphine (ethylmorphine) is a derivative of morphine with analgesic and antitussive effect. It acts by activating the opioid receptors and thus has a direct influence on the CNS system.

Gefapixant is a selective antagonist of the P2X3 receptor. P2X3 receptors are ATP-gated ion channels found on sensory C fibres of the vagus nerve in the airways. C fibres are activated in response to inflammation or chemical irritants. Blockade of ATP signalling through P2X3 receptors reduces excessive sensory-nerve activation and excessive cough induced by extracellular ATP.

Hydrocodone is a semisynthetic narcotic analgesic and antitussive with multiple actions qualitatively similar to those of codeine. Most of these involve the central nervous system and smooth muscle.

Levodropropizine is a drug provided with a mainly peripheral tracheobronchial antitussive effect together with an antiallergic and antibronchospastic effect.

Normethadone is a derivate of opioid analgetic methadone, used as component of antitussive drops.

Noscapine is a benzylisoquinoline alkaloid from plants of the poppy family, without painkilling properties. Noscapine is often used as an antitussive medication. Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics. Noscapine, and its synthetic derivatives called noscapinoids, are known to interact with microtubules and inhibit cancer cell proliferation. Mechanisms for its antitussive action are unknown, although animal studies have suggested central nervous system as a site of action. Furthermore, noscapine causes apoptosis in many cell types and has potent antitumor activity against solid murine lymphoid tumors (even when the drug was administered orally) and against human breast and bladder tumors implanted in nude mice. Antifibrotic effect of noscapine based on novel mechanism, which it shows through EP2 prostaglandin E2 receptor-mediated activation of protein kinase A.

Oxeladin is a highly potent and effective drug used to treat all types of cough of various etiologies. It is not related to opium or its derivatives, so treatment with oxeladin is free of risk of dependence or addiction.

Pentoxyverine is a non-opioid antitussive used to prevent cough caused by common cold. It is used as an active ingredient of several oral over-the-counter cough suppressants alone or in combination with other medications, especially decongestants.

Pholcodine is an opioid that has been widely used for the treatment of non-productive cough in children and adults. Pholcodine is a cough suppressant with mild sedative but little analgesic activity. Additionally pholcodine is a marker for sensitization to neuromuscular blocking agents (NMBA) and is intended for use as a diagnostic tool in NMBA-induced anaphylaxis.