Serotoninergic agents

The discovery of natural products of therapeutic value, and especially serotoninergic agents, from this very large family is most probable. 

Many reports have linked childhood hyperactivity to impaired central serotonin functions.89 In animals, the occurrence of a behavioral syndrome consisting of hyperactivity, stereotyped movements, and increase of temperature has been induced by L-tryptophan, as a serotonin precursor, by serotonin reuptake inhibitors, and by MAOIs.90 Most of these manifestations can be blocked specifically by pretreatment with an inhibitor of serotonin synthesis. In humans, the association of myoclonus, diarrhea, confusion, hypomania, agitation, hyperreflexia, shivering, incoordination, fever, and diaphoresis, when patients are treated with serotoninergic agents, could constitute a "serotonin syndrome." Such cases of serotonin syndrome were reported after treatments with L-tryptophan, MAOIs, serotonin reuptake inhibitors, and tricyclics, alone or in association. 

Smejkal-Jagar, L. and Botanic, M. (1994) Serotonin, serotoninergic agents and their antagonists suppress humoral immune reaction in vitro. Res. Exp. Med. Berl., 194, 297-304. 

Anxiolytics are compounds that act primarily to refleve the symptoms of anxiety although such agents can also be used as anticonvulsants, sedatives, hypnotics, and anesthetic agents (see Anesthetics). The principal class of anxiolytics, the BZs, shows dependence HabiUty (5) whereas newer agents such as buspkone [36505-84-7] and ritanserine [8705-43-2] produce antianxiety effects via central serotoninergic systems (6). 

Appetite suppressants have been widely used as an adjunct to dietary restriction and sympathomimetic amines have traditionally been used for this purpose. These agents have not proven particularly useful and frequentiy cause unacceptable side effects, hence their popularity has been waning for several years. The most promising newer dmgs work through a serotoninergic mechanism and hold considerable promise at least for certain obese patients. 

In regard to the experimental evidence available, a substantial number of reports on the chemical constituents of the plant are available, but much less work has been done with the pharmacological properties. Kasture et al., however, made the important observation that a triterpene isolated from R. cordifolia induces anxiety in rodents, an effect accompanied with an increase in serotonin contents in the brain (30). An interesting development from that observation would be to explore further the molecular-pharmacological pathway and the effect of this agent on the serotoninergic system because terpenes, compared with indole alkaloids, are seldom reported for serotoninergic activities. 

The introduction of novel anxiolytic agents such as buspirone, which interacts with the serotoninergic system, has suggested that serotoninergic fibers may be the final pathway through which anxiolytic effects are expressed. 

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