Antitussive agents

Opium is the dried, powdered sap of the unripe seed pod of Papaver somniferum, a poppy plant indigenous to Asia minor. Theophrastus described its medical properties in the third century BC, but the Sumerians, ca BC 4000, probably perceived its utility. Arab physicians knew of the dmg, and Arab traders carried it to the Orient where it was used as a treatment for dysentery. Paracelsus is credited with repopularizing the dmg in western Europe in the early sixteenth century by formulating opium into "laudanum", which is still in use. More than 20 different alkaloids (qv) of two different classes comprise 25% of the weight of dry opium. The benzylisoquinolines, characterized by papaverine [58-74-2] (1.0%), a smooth muscle relaxant, and noscapine [128-62-1] (6.0%), an antitussive agent, do not have any analgesic effects. The phenanthrenes, the second group, are the more common and include 10% morphine (1, = R = H), 0.5% codeine [76-57-3], C gH2 N03, (1, R = H, R = CH3), and 0.2 thebaine [115-37-7], C 2H2 N03, (2). 

Codeine, mol wt 299.3, is a significantly less potent analgesic than morphine, requiring 60 mg (0.20 mmol) to equal the effectiveness of 10 mg (0.04 mmol) of morphine. However, codeine is orally effective, and it is less addictive and associated with less nausea than morphine. Codeine is used as an antitussive agent, although newer, nonaddictive agents are preferred (see Expectorants, antitussives, and related agents). 

Condensation of the substituted phenethyl bromide, 18, with piperazine can be stopped at the monosubstituted amine (19). Reaction of this amine with propiophenone and formaldehyde in a Mannich reaction affords eprazinone (20) an antitussive agent. 

Reaction of p-chlorobenzylmagnesium chloride with the Mannich product from 2-butanone (177) produces the antitussive agent, clobutinol (178). 

Other applications include bioequivalent measurements of bromazepam, an anticonvulsant, in human plasma. The lower limit of quantitation (LLOQ) was 1 ng/mL (Gongalves et al. 2005). Kuhlenbeck et al. (2005) studied antitussive agents (dextromethorphan, dextrophan, and guaifenesin) in human plasma LLOQ values were 0.05, 0.05, and 5 ng/mL, respectively. Other compounds studied were nucleoside reverse transcriptase inhibitors, zidovudine (AZT) and lamivudine (3TC) (de Cassia et al. 2004) and stavudine (Raices et al. 2003) in human plasma, and paclitaxel, an anticancer agent, in human serum (Schellen et al. 2000). 

An antitussive agent, then, is a drug that suppresses or prevents cough. Codeine and dextromethorphan are the most commoniy used antitussives. Other opioids are also effective antitussive agents, but are not used as medicines to suppress cough. 

The opioids contain natural and synthetic compounds that are medicinally used as analgesic, antidiarrheal, and antitussive agents. Opioids are CNS depressants and decrease blood pres-... 

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 ). 

Matthys, H., Erhardt, J., Ruhle, K.H. [Objectivation of the effect of antitussive agents using tussometry in patients with chronic cough], Schweiz. Med. Wochenschr. 1985, 115, 307-311. 

The calcium ion antagonists nifedipine 21829-25A] (62), verapamil [52-55-9] (63), and flunarizine [52468-60-7] (64) exhibit antitussive effects in a dose-dependent manner in guinea pigs (91). Pretreatment with a subthreshold dose of nifedipine also markedly increased the antitussive effects of morphine, dihydrocodeine, and dextromethorphan. However, none of the calcium ion antagonists are used clinically as antitussive agents. They are used in the treatment of angina and hypertension (see Cardiovascularagents). 

Konrad D, Sobetzko D, Schmitt B, Schoenle EJ. Insulin-dependent diabetes mellitus induced by the antitussive agent dextromethorphan. Diabetologia 2000 43(2) 261-2. 

Chinese medical practitioners in the 15th century recommended ephedra as an antipyretic and antitussive agent. Modem physicians use intravenous ephedrine for the prophylaxis and treatment of hypotension caused by spinal anesthesia, particularly during cesarean section (see Chapter 29). 

The genus Achillea is distributed in temperature regions of the Northern Hemisphere, especially in Europe and Asia. Achillea millefolium is a species frequently used in Europe and America alike. Many species of this genus are rich in essential oil, SQLs, and flavonoids. It is used internally as an antitussive agent and externally as an analgesic. 

The dextrorotatory isomer of 3-methoxy-A-methylmorphinan, a synthetic morphine derivative (Roinilar hydrobromide , Tusilan ) is employed exclusively as an antitussive agent. Its levorotary isomer (in the form of the 3-hydroxy tartrate) is described next. These compounds differ from morphine chemically in lacking the -O- bridge between carbons 4 and 5, the OH group at C6, and... 

Dextromethorphan (Romilar) is the dextroisomer of the methyl ether of levorphanol. Unlike its levorotatory congener, it possesses no significant analgesic property, exerts no depressant effects on respiration, and lacks addiction liability. It is an antitussive agent with a potency approximately one half that of codeine. 

Morpholinoethylmorphine is known as pholcodine and has found wide application as an antitussive agent. Other series with basic (e.g., 1, R = CH2 CH2ND) or urethane (e.g., 1, R = CONHR ) 3-0- side chains have been reported/96 ... 

R = Me) demonstrated that it lacked analgesic responses. The corresponding methyl ether, 49 (R = OMe R = Me), however, proved to be a clinically useful antitussive agent known as dextromethorphan or Romilar. ... 

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 ... 

Glaucine is a non-narcotic antitussive agent. The D-isomer of glaucine is an alkaloid from Glaucium flavum Grantz, a species of Papaveraceae. It is better tolerated in doses claimed to be equieffective with codeine. Glaucine (30 mg capsules 3 times daily for 28 days) caused mild constipation in five patients (1). 

Gastpar H, Criscuolo D, Dieterich HA. Efficacy and tolerability of glaucine as an antitussive agent. Curr Med Res Opin 1984 9(l) 21-7. 

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