Benzylisoquinoline alkaloids pharmacology

A large number of alkaloids have been converted to quaternary salts and examined pharmacologically. The quaternary derivatives of certain bis-benzylisoquinoline alkaloids, which are closely related structurally to one class of curare alkaloids, are potent curarizing agents. Quaternary salts of cinchona alkaloids are effective and have been used in clinical investigations. Quaternary salts of many other alkaloids have been shown to exhibit curariform activity. 

The pharmacological activity of certain bisbenzylisoqui-noline alkaloids has been reviewed (Buck, 1987 Schiff, 1987). Many of these compounds have weak to moderate antimicrobial activity. Two types of bisisoquinoline alkaloids possess antitumor activity. These are bisbenzylisoqui-noline and aporphine-benzylisoquinoline alkaloids [e.g., tetrandrine (99) and thalicarpine (100), respectively]. Both have pronounced side effects (Cordell, 1978b). 

The capsules and stems of Papaver somniferum contain opiate alkaloids essential in medicine. They are classified into two groups, phenanthrene types (morphine, codeine, thebaine) and benzylisoquinoline types [papaverine and noscapine(narcotine)]. These two types of alkaloids show sharply specific pharmacological properties. It is noteworthy that morphinane alkaloids are formed from (-)-(/ )-reticuline, whereas most other alkaloids derive from (-l-)-(5)-re-ticuline 11). 

The isoquinoline alkaloids constitute perhaps the largest single group of alkaloids known. Generally speaking, they exert their most pronounced pharmacological actions on the central nervous system and on smooth muscle. With respect to the latter, the benzylisoquinoline derivatives... 

The pharmacological effects of this complex mixture of alkaloids in opium may, in some respects, be more beneficial than the effects of an individual alkaloid. The effect of opium in the treatment of diarrhoea is better than that of either morphine or codeine given individually. It is possible to calm the gastrointestinal tract with a dose which contains only half of the dose which would be necessary for morphine alone. The combination of the increase in stretch reflex caused by morphine and the inhibition of increased peristaltic action by papaverine leads to a better therapeutic effect. The increase in muscle tone due to morphine is reduced by papaverine, and other benzylisoquinolines also participate in this tranquillisation of the g.i. tract. In the normal 50 mg dosage of opium used for the treatment of diarrhoea there is about 5 mg of morphine, 0.5 mg of papaverine and 3 mg of nos-capine which contrasts markedly with a dose of 100—200 mg of papaverine if this were given alone. The analgaesic activity of opium is due mainly to the morphine present, as the levels of codeine, neopine and papaverine are relatively small. The respiratory depression effect of opium is also due to the morphine content and the antagonistic effects of noscapine and narcotoline are not so pronounced. Thus the main use of opium in medicine is for the treatment of diarrhoea. 

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