Other Potential Antitussives

Codeine, one of the principal alkaloids of opium, has an analgesic efficacy much lower than other opioids, due to an extremely low affinity for opioid receptors. It is approximately one-sixth as potent as morphine. It has a low abuse potential. In contrast to other opioids, with the exception of oxycodone, codeine is relatively more effective when administered orally than parenterally. This is due to methylation at the C3 site on the phenyl ring (Figure 7.3), which may protect it from conjugating enzymes. It is used in the management of mild-to-moderate pain, often in combination with non-opioid analgesics, such as aspirin or paracetamol. It is valuable as an antitussive and for the treatment of diarrhoea. Side effects are uncommon and respiratory depression, even with large doses, is seldom a problem. 

In healthy subjects, menthol vapor inhibits citric acid induced cough, unlike other aromatic oils which were used to act as placebos (Packman and London 1980 Morice et al. 1994). Unfortunately no properly designed clinical trials of vaporized menthol against cough seem to have been done, possibly for lack of an adequate placebo, but the basic studies suggest that it is potentially an active antitussive. 

Along with other ion channel modulators, menthol is recognized as a potential novel therapy for the treatment of chronic cough (Morice et al., 2004). It is not clear whether the antitussive activity of menthol is due solely to its stimulation of airway cold receptors it may also involve pulmonary C- bers (a percentage of which also express TRPM8) or there may be a sped c interaction with the neuronal cough re ex. 

In relation to their chemical structure and action, they can be classified into two categories. The first are phenanthrene alkaloids and are under international control morphine (MO), codeine (COD), and thebaine (TB), which act on the central nervous system and are used as analgesics, narcotics, and potentially addicting compounds (pain relievers). Heroin is synthesized from MO. The second group is isoquinoline alkaloids Papaverine (PV) and narcotine (also known as noscapine). Narcotine acts only to relax involuntary smooth muscles, for which it is considered an antitussive, and lacks addictive, analgesic, respiratory, narcotic, depressant, and sedative properties. Next to MO, which constitute about 10% by weight of raw opium, is the second most abundant alkaloid present in opium. The three last alkaloids (PV, narcotine, and narceine) are not under international control specially, narcotine and narceine which have scarcely any medical or other uses. Consequently, the five economically significant alkaloids of opium are MO, COD, TB, PV, and narcotine. 

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