Acting Antitussive Agents

Examples Benzonatate Carbetapentane citrate Noscapine Levopropoxyphene napsylate Dextromethorphan hydrobromide Pholcodine. 

Benzonatate may be prepared by the transesterification of ethyl- -(butylamino) benzoate with a polyethyleneglycol monomethyl ester (b.p. 180-220°C) at 1 mm Hg. The reaction is carried out in vacuo whereby a thin stream of xylene is made to pass through it. After complete removal of the traces of moisture and volatile components, a solution of sodium methoxide in methanol is added to the reaction mixture. The contents are heated under vacuo, after addition of xylene, for 2 to 3 hours at 100°C. The crude benzonatate thus obtained may be purified by suitable means. 

It is a potent antitussive agent. It usually acts by inhibiting transmission of impulses of the cough reflex in the vagal nuclei of the medulla and predominantly depresses polysynaptic spinal reflexes. It is regarded as a cough suppressant acting both centrally and peripherally 

2-[2-(Diethylamino) ethoxy] ethyl 1 -phenylcyclopentane-carboxy eitrate (1 1) NF Xlll Toclase (Pfizer). 

It may be prepared by the condensation of 1-phenyl-cyclopentane carbonyl chloride with 2-(diethylaminoethoxy) ethanol to yield carbetapentane base by the elimination of a mole of hydrogen chloride. The base is dissolved in ethanol and treated with a equimolar portion of citric acid to give the official compound. 

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In Japan, 3,17-dimethylmorphinan phosphate (Dimemorfan) has been marketed as a centrally acting antitussive agent,(54) and the related (+)-3-ethyl-17-methyl analog is reported in the patent literature to have analgesic and antitussive properties/543 ... 

It was recently recognized that opioid receptor agonists have antitussive effects [31]. Morphine (Fig. 7) is a potent p opioid receptor agonist that exhibits marked antitussive effect, and it has been used for the treatment of severe coughs. Codeine (Fig. 7) is one of the most reliable centrally acting antitussive agents its antitussive... 

Expectorants and antitussive agents may be broadly classified into the following three categories (/) Sedative Expectorants (n) Stimulant (Irritant) Expectorants iii) Centrally Acting Antitussive Agents. 

Name two drugs that act as centrally acting antitussive agents and are analogues of morphine. Discuss the synthesis of one such compound. 

It is a methyl ester of morphine and less potent analgesic than morphine. It is widely used as antitussive agent. Pholcodeine is also used as antitussive agent and causes less constipation (Details are given in chapter Drugs acting on respiratory system ). 

Current antitussives are broadly divided according to their site of action as either central or peripheral, although many act to some extent at both locations. Centrally acting antitussives act within the central nervous system (CNS) to suppress central cough pathways and comprise the majority of currently used drugs. However, opioids, which are gold standard antitussive agents, suffer from numerous... 

Most conventional antitussives are thought to act at brainstem level, and several mediators and transmitters involved in cough have been identified here (Chen et al. 2008 Takahama et al. 2008), offering possible sites of action for antitussive agents. Other afferent inputs, for example, from the esophagus, nose, and ear, are known to modulate the cough reflex initiated from the lower airways (Hanacek et al. 2006), and some of these could be activated by herbal and other CAM treatments. 

Researchers in the field of conventional medicine are now searching intensively for antitussive agents that act on the membrane receptors for cough sensors in the airways (peripherally acting antitussives) (Chung 2006, 2007,2008 Barnes 2007), but similar studies do not seem to have been conducted for herbal CAM therapies. 

Dextromethorphan is the methylated dextro-isomer of levorphanol. Unlike the L-isomer, it has no analgesic properties. Dextromethorphan acts on the central nervous system (CNS) to elevate the cough threshold. It retains only the antitussive activity of other morphine derivatives. Administration of dextromethorphan may be associated with histamine release. Dextromethorphan is often present in multisymptom products with a combination of ingredients. Toxic effects of concurrent agents such as antihistamines, decongestants, analgesics, and/or alcohol may be exhibited. 

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