Antitussive properties

Molecular modifications of the morphine skeleton have produced numerous derivatives with antitussive properties, some of which have become commercially significant. Ethyknorphine [76-58-4] (29), a simple homologue of codeine, is prepared by ethylating morphine. It is pharmacologically similar to codeine but is seldom used clinically. Pholcodine [509-67-1] (30), the morpholinoethyl derivative of morphine, is used as an antitussive in a number of European countries. It is about one and a half times as potent as codeine, has Htde or no analgesic activity, and produces minimal physical dependence. The compound is prepared by the amino alkylation of morphine (48). 

Bromination of the methyl group of (249) with A -bromosuccinimide, followed by reaction with excess secondary amine gave (250) which shows combined analgesic and antitussive properties. The Reformatsky reaction has also been used for the preparation of 2-amino-ethyl 3,3-diaryl-3-hydroxypropanates (251) as well as their dehydration products. The propene amides (252) have also been prepared for pharmacological evaluation. In l-methyl-3-bis (2-thienyl)-... 

It is medicinally used from Korea to Cambodia, Laos, and Vietnam. In Korea, the plant is used as an aphrodisiac for males and the elderly. In Japan, a decoction of the root is drunk to treat cough, invigorate, and treat tuberculosis. In Taiwan, the plant is an external remedy for snake bites. In Cambodia, Laos, and Vietnam, the roots are used to treat bronchitis, amnesia, and to stimulate memory and urination. The antitussive property is very probably owed to polygalasaponins, which are known to abound in the plant (24-26). It would be interesting to know whether the tonic properties mentioned here are owed to serotoninergic mechanisms. What is the alkaloidal content of this herb ... 

Hydrocodone exhibits expressed analgesic and antitussive properties, which make up its primary clinical use. It may cause dependence and addiction. Synonyms for this medication are dicodid, detussin, vicodin, and others. 

Another drug with antitussive properties is Libexin (241). Butalamine (242) causes coronary vasodilation, local anesthesia, analgesia, a papaverine-like action in duodenal preparations and smooth muscle relaxation <69JPP474>. 

It is dextro isomer of propoxyphene which is an analgesic and possesses antitussive property. It has low analgesic activity even half of codeine. It is metabolized in Uver. Side effects include vomiting, epigastric distress and sedation. The demethylated metabolite of propoxyphene is cardiotoxic. It is used in the treatment of mild type of pain. 

Analgesic efficacy and clinical use Codeine (Honig and Murray, 1984) has a morphine-like action profile with analgesic and antitussive properties. As compared to morphine the analgesic potency is 5—1 Ofold lower. The compound is used for the treatment of mild to moderate pain and for cough inhibition (Eccles,1996). 

Analgesic efficacy Dihydrocodeine has codeine-like analgesic and antitussive properties and is used for the treatment of moderate to severe pain (Edwards et al., 2000) and as antitussive (Matthys et al., 1985). 

Analgesic efficacy and clinical use Levomethadone like racemic methadone is a potent and long-acting opioid analgesic and can be used for the treatment of moderate to severe pain (Jamison, 2000 Davis and Walsh, 2001). It has an action profile similar to morphine and has significant antitussive properties, for which it is used in terminal lung cancer. The long duration of action makes the compound suitable for substitution treatment of opioid addiction (Joseph et al., 2000 Pallenbach, 2002). For practical and economic reasons the racemate instead of the levo-enantiomer is used in addicts. 

Slippery elm has demulcent, emollient, nutritive, and antitussive properties. Traditionally, it is used for inflammation or ulceration of the stomach or duodenum, convalescence, colitis, diarrhea, and locally for abscesses, boils, and ulcers (as a poultice). 

N-oxides of morphine and several morphine derivatives have been prepared by the action of isopropanol/H202 on the appropriate tertiary base.(156) At best, the N-oxides were weak analgesics, but dihydromorphinone N-oxide and codeine N-oxide did exhibit good antitussive properties/157 ... 

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 ... 

The (—)-morphinans (i.e., those configurationally related to morphine) are responsible for all the antinociceptive properties of the racemate. In addition, such compounds tend to have parallel respiratory depression levels and PDCs. In (+)-series (e.g., dextromethorphan), clinically useful antitussive properties are encountered, again following the separation of biological activities noted in 4,5-epoxymorphinan optical antipodes. 

The kinetics and mechanism of hydrolysis of narcotine and of lactonization of narcotic add have been studied/ Another report deals with the instability of bicuculline under physiological conditions/ 8-Ethylnarcotoline hydrochloride had antitussive properties similar to codeine phosphate but the hydrochlorides of narcotoline and 8-benzylnarcotoline were weaker/ ... 

Hydrocodone is used in small animal veterinary practice for the management of pain and for its antitussive properties. Hydrocodone should be used with... 

Although it is more toxic than morphine on a weight basis, methadone is more potent. On resolving the racemic compound, the (-) form was found to possess most of the opioid activities. The dextrorotatory isomer retains basically only the antitussive property (the commercial product is the racemic form). The potential advantages of methadone over morphine is its effectiveness via the oral route and considerably longer half-life (24-36 vs. 2- hours). This feature, particularly, has led to the drug s extensive use in the treatment of heroin addicts to suppress the latters abstinence syndrome by maintenance of patients with methadone only. 

Diphenhydramine and chlorcyclizine are antihistaminic agents that also have antitussive properties. Dimethoxanate (Cothera) and pipazethate (Theratuss) are phenothiazine derivatives without analgesic but with weak antitussive and local anesthetic properties. 

Tolerance to codeine develops very slowly, and the addiction liability is far less than that observed for morphine. Most narcotics such as morphine, codeine, dihydrocodeine, methadone, and levorphanol have antitussive properties. Codeine is used primarily because its addictive liability is low and it is effective orally. The antitussive doses of narcotics are lower than the doses used for analgesic purposes. 

Besides its antitussive property, recent studies have shown that dextromethorphan has anticonvulsant and neuroprotec-tive properties. Because dextromethorphan interacts with N-methyl-D-aspartate (NMDA) or sigma receptors, it may become important in ameliorating the cerebrovascular and functional consequences of global cerebral ischemia. 

Bromination of 86a by iV-bromosuccinimide took place at the allylic position rather than on the thiophene rings the resulting bromomethyl compound (86b), on reaction with a variety of secondary amines, gives products (86c) with analgesic and antitussive properties.113 Nucleophilic substitution of chlorine from chloromethyl derivatives has been effected by... 

Interest in dithienylalkanes of potential pharmacological importance was aroused by the discovery that some 3-dialkylamino-l,l-bis(2-thienyl)but-l-enes possess analgesic activity.116 Compounds 91, termed thiambutenes, are prepared by dehydration of carbinols of general formula 92. Considerable variations in the substituents have been made in the search for greater activity and for a reduction in undesirable side effects often, these variants have both analgesic and antitussive properties. Substances with obvious structural similarities to 91 and 92, namely, the thiophene analog of methadone (93) and of isomethadone, have also been prepared.63,107... 

It is a potent narcotic analgesics having actions quantitatively comparable to morphine though slightly less potent than morphine as an analgesic. Besides, it exerts sedation and antitussive properties. It also helps in the temporary maintenance and treatment of dependence on narcotic drugs, because its withdrawal syndrome has slow onset and much less intense than mrophine. 

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