Benzonatate is an antitussive that is FDA approved for the symptomatic relief of cough. It acts peripherally by anesthetizing the stretch receptors located in the respiratory passages, lungs, and pleura by dampening their activity and thereby reducing the cough reflex at its source. Common adverse reactions include nausea, oral hypoesthesia, throat symptom, numbness, dizziness, headache, sedation, somnolence. Benzonatate is chemically related to anesthetic agents of the para-amino-benzoic acid class (e.g. procaine; tetracaine) and has been associated with adverse CNS effects possibly related to a prior sensitivity to related agents or interaction with concomitant medication.

Guaifenesin is an expectorant the action of which promotes or facilitates the removal of secretions from the respiratory tract. The precise mechanism of action of guaifenesin is not known; however, it is thought to act as an expectorant by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi. In turn, this may increase the efficiency of the cough reflex and facilitate removal of the secretions. Guaifenesin is over-the-counter drug for the treatment of cough and common cold.

Chlophedianol (Clofedanol) is a centrally-acting cough suppressant, although the mechanism of action is not known. It is available in Canada under the trade name Ulone. It is not available in the United States. Chlophedianol (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.

Dextromethorphan is a non-narcotic morphine derivative widely used as an antitussive for almost 40 years. It has attracted attention due to its anticonvulsant and neuroprotective properties. It is a cough suppressant in many over-the-counter cold and cough medicines. In 2010, the FDA approved the combination product dextromethorphan/quinidine for the treatment of pseudobulbar affect. Dextromethorphan suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. Dextromethorphan shows high-affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist and acts as a non-competitive channel blocker. It is one of the widely used antitussives and is used to study the involvement of glutamate receptors in neurotoxicity. Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist. The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown. Dextromethorphan should not be taken with monoamine oxidase inhibitors due to the potential for serotonin syndrome. Dextromethorphan is extensively metabolized by CYP2D6 to dextrorphan, which is rapidly glucuronidated and unable to cross the blood-brain barrier.

Camphor is a bicyclic monoterpene ketone found widely in plants, especially cinnamomum camphora. Topically, camphor is used to relieve pain. It has been used to treat warts, cold sores, hemorrhoids, and osteoarthritis. It has also been applied topically as an analgesic and an antipruritic. It has been used as a counterirritant, and to increase local blood flow. Camphor has frequently been used topically to treat respiratory tract diseases involving mucous membrane inflammation. It is sometimes used topically to treat cardiac symptoms. Camphor is also used topically as an eardrop, and for treating minor burns. In inhalation therapy, camphor is used as an antitussive. Orally, camphor is used as an expectorant, antiflatulent, and for treating respiratory tract diseases. Today, most camphor is synthetic. It is approved by the FDA as a topical antitussive. Camphor is produced synthetically from the oil of turpentine. It has been used for centuries for its medicinal features, in religious rituals, and in cooking. It is no longer used as pesticide. In 1982, the US Food and Drug Administration restricted commercial products intended for medicinal use to contain <11% camphor.

Dextrorphan is an active metabolite of dextromethorphan, is an antitussive agent, which was found in cough medicines. Dextrorphan is a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, sigma 1 receptor agonist, so as is an agonist of mu and kappa opioid receptors. In addition was found, that dextrorphan possessed anticonvulsive and neuroprotective effects.

Moguisteine is a non-narcotic antitussive compound. Moguisteine demonstrated inhibitory effect on rapidly adapting irritant receptors that could account for the antitussigenic effect of this compound. Furthermore, it is possible that ATP-sensitive K(+) channels may be involved in the anti-tussive effect of peripherally acting non-narcotic moguisteine. The drug did not show any toxic effect on the dams and their fetuses, nor did it have any teratogenic effect in either of the tested species. Finally, moguisteine had no adverse effects, either on parturition or on peri-and postnatal survival and/or development of the offspring. It was reported that moguisteine to be effective in reducing cough frequency in chronic cough of bronchitis and COPD. It was recommended for the short-term symptomatic relief of coughing. Preregistration of moguisteine in Italy is discontinued.

Medazomide (medazonamide) is an antitussive drug.

CP 99994 dihydrochloride have shown the compound to be a potent, selective and competitive NK-1 receptor antagonist. In preclinical studies, CP 99994 decreased cough number, peak abdominal activity, and peak tracheal pressure, without affecting baseline respiration. But in clinical trial administration of CP 99994 over 2 h does not significantly inhibit hypertonic saline-induced bronchoconstriction or cough in subjects with mild asthma. CP 99994 significantly suppressed acute postoperative pain at 90 min after surgery.

Verticinone is a major alkaloid isolated from the bulbus of Fritillaria ussuriensis. Verticinone was rapidly absorbed, widely distributed in most tissues, and metabolized extensively before excretion. Verticinone has antitumor effects - treatment with verticinone can induce cancer cell apoptosis and autophagy via modulating the production of metabolites, which are supportive of carcinoma cell proliferation. Due to the potent antitussive activity and no addictive effect, verticinone seems to be a promising potential antitussive drug. Verticinone is expected to become a potentially novel sedative-analgesic agent without producing tolerance and dependence.