Neuropharmacology of drugs affecting food intake.

The importance of the central monoamines NE, DA and 5-HT in ingestive behavior has inevitably resulted in considerable effort being expended in attempting to implicate these monoamines in the mechanism of action of anorectic drugs. The statements that amphetamine-induced anorexia is unlikely to be due to central serotoninergic systems and that central noradrenergic and dopaminergic systems are not implicated in the appetite suppressant effect of fenfluramine are in all probability correct. However, to attribute the ability of drugs to decrease food intake unequivocally to a specific effect on central monoaminergic systems is almost certainly an oversimplification, due to the fact that other putative neurotransmitters, such as GABA and peptides, play a critical role in eating. This can be achieved either directly or by modulating the release of other transmitters. An added complication in attempting to correlate a specific neurochemical process to a behavioral effect, such as anorexia, is the complexity of the central actions of the drug. At best, a predominant but not an exclusive process can be identified. Perhaps the in-built constraint of attempting to correlate a specific neurochemical effect to the desired action of a drug is accountable for the absence of a second generation of centrally acting anorectic drugs. Dramatic progress has been made in elucidating the factors involved in ingestive behavior over the last 5-10 years. This information should, and must, provide the catalyst for more efficacious anorectic drugs because obesity represents one of the few major diseases for which adequate drug therapy does not exist.