Some common molecular patterns in pharmacodynamic drugs

2 Some common molecular patterns in pharmacodynamic drugs 

It is one of the curiosities of nature that many plants find it convenient to excrete waste nitrogen in molecules that have patterns which affect vertebrate nerve and muscle, although these two kinds of tissue are completely lacking in the plant kingdom. Alkaloids are typical waste products of plant metabolism, allowed to accumulate only in those parts of the plant which can easily be shed, such as the bark, leaves, and fruit. The majority of alkaloids are biologically inert in mammals. Of the 25 alkaloids of opium, only 4 show any effect on Man. 

It may at first seem bold to suggest that all these substances, whether alkaloids, neurotransmitters, or the newer synthetic drugs, are acting on a few, chemically similar, receptors. The pattern itself allows of considerable variation without loss of a particular biological effect, e.g. local anaesthetics may be either type (7.7) or (7.2), the number of connecting carbon atoms may be two or three, and these may carry small substituents such as methyl-groups. This points to a conclusion that the receptors of vertebrates have not so great a specificity for their substrates as many enzymes have (Ariens, 1960 Fastier, 1964). 

In line with this conclusion is the fact that few pharmacodynamic drugs have complete biological specificity. They usually give results suggestive of combination with a single, fairly specific, receptor, but in addition show a number of 

Although the specificity of receptors is not so strict as that of the most important anabolic and catabolic enzymes, it is at least as strict as the degrad-ative enzymes of microsomes (see Section 3.5). Thus at ganglia, nicotine (but not muscarine) can take the place of acetylcholine, whereas at postganglionic parasympathetic synapses, muscarine (but not nicotine) can take its place (see Table 7.1). Further specificity is shown in acetylcholine antagonism, for which tubocurarine is specific at the neuromuscular junction, hexamethonium at ganglia, and atropine at parasympathetic postganglionic synapses. 

It is one of the curiosities of nature that many plants find it convenient to excrete waste nitrogen in molecules that have patterns which affect 

Further, this pattern turns up often in contemporary pharmacodynamic agents, especially in local anaesthetics, antihistamines, anti-emetics, tranquillizers, and in drugs intended to replace one or more uses of atropine. This is not a chance occurrence, because Fourneau and Bovet, 

Although it seems that receptors have only a moderate specificity, it should still be possible to find specific drugs by (a) arranging their ionic (Chapter 10) and lipophilic (Section 3.2 and Appendix II) properties to give them the best possible access to the site, and (b) providing them with such blocking groups as sterically prevent their access to other sites (Fastier, 1964). At the same time, the structure should be kept as simple as possible to avoid side-effects. 

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