Presidential Address

Dr. Saletu, Dean Kraupp, Professor Berner, Esteemed Colleagues:

Welcome to the Eleventh Congress of the Collegium Internationale Neuropsychopharmacologicum. We anticipate a week in which our brains will be filled with new information, in which our stomachs will be filled with good food, and in which our spirits will be lightened by the gemütlichkeit that no visitor to Vienna can escape.

The enormous job of putting together a meeting such as this has undoubtedly involved more persons than I could possibly name. We owe especial thanks to Professor Peter Berner for arranging the excellent scientific program that awaits us and to Dr. Berndt Saletu for making the innumerable arrangements that were necessary to accommodate us physically. Such a vast undertaking is not expected to run perfectly so that if any of you have encountered difficulties along the way, please understand the complexity of the organization of such a Congress. We also wish to thank our numerous supporting members (all of whom have been recognized on the program, I hope) without whose support this Congress would have truly been impossible.

Approximately twenty-five years ago, the modern era of neuropsychopharmacology began with the successful treatment of schizophrenia with chlorpromazine. The immediate past-President of the C.I.N.P., Professor Pierre Deniker, was a participant in this epoch-making event, which led, among many other things, to the formation of the C.I.N.P. twenty years ago. Few of us would have guessed then how well this new, multidisciplinary field would fare over the succeeding years. Our field has attracted the interest of clinicians and basic scientists from many specialties and many disciplines. Meetings such as this foster the communication between such diverse groups necessary for the integration of knowledge that will allow us better to understand and better to treat disorders of the central nervous system, whether manifested by psychiatric, neurologic, endocrine or other disorders.

We may well be proud of the many new drugs that have been developed during the past quarter century that have ameliorated the course of these disorders for many patients. Present antipsychotic drugs embrace perhaps 200 or more compounds marketed throughout the world, involving a multiplicity of chemical structures. The tricyclic antidepressants are less numerous, but in recent years the number of chemical structures has been expanded to include new bicyclic and tetracyclic structures. A new division of monoamine oxidase inhibitors may allow more specific utilization of these drugs for treating depression and Parkinson’s disease. The benzodiazepines have advantages that have made most of the barbiturates obsolete; indeed, their rapid proliferation may make this class of compounds even more plentiful than was the case with barbiturates. Lithium has replaced bromide as an ion therapy in psychiatry; its unique ability to modulate the course of manic-depressive disorder being a far greater contribution to treatment than anything offered by the bromide ion.

The drug-induced model of Parkinson’s disease ultimately led to a completely new approach to treating this disorder. Treatment directed at increasing dopaminergic transmission, either with levodopa or with amantadine, has been added to the more conventional approach of treating with drugs that reduce cholinergic activity. Levodopa-induced dyskinesia and tardive dyskinesia from antipsychotic drugs both may be partial models for Huntington’s disease. These models have stimulated new approaches to the treatment of this disorder, either by decreasing dopamine receptor sensitivity or by increasing cholinergic activity. We were well advised to use the compound term, neuropsychopharmacology, for describing our field and for naming this college some two decades ago.

Progress in the basic sciences of neuropharmacology has been even more impressive than it has been in the clinical applications. Twenty-five years ago, the only established central nervous system neurotransmitter was acetylcholine. Soon after the introduction of antipsychotic drugs, the so-called biogenic amines, serotonin, norepinephrine and dopamine, became considered as putative neurotransmitters. The mechanisms by which these biogenic amines are synthesized, transported, stored, released, recaptured and metabolized have been rather well worked out. Their selective distribution in the brain was delineated by simple yet elegant histochemical techniques. The effects of drugs on these systems led to the formulation both of the amine hypothesis of depression and the dopamine hypothesis of schizophrenia. These hypotheses, among others, can be tested in various ways, the first time that this essential aspect of the scientific method has been applicable to study of the pathogenesis of psychiatric disorders. More recently, attention has been focused on receptors for these neurotransmitters and the changes that may occur in these receptors during treatment with psychotherapeutic drugs.

One might say that the many advances in the basic sciences are overwhelming. Scarcely do we begin to understand the possible function of one or two neurotransmitters before additional ones are discovered. We are still uncertain about the role in the brain of some old neurotransmitters, such as histamine and epinephrine, not to mention the many new biogenic amines found in the brain that may have a role as neurotransmitters. Amino acids and peptides are present in abundance in the brain, and like the biogenic amines, are selectively distributed. The various endorphins are currently of greatest interest, as their action may relate to that of a classic drug, morphine, that acts on the central nervous system. Far less clear is why gastrointestinal hormones, such as gastrin and somatostatin, should be in the brain, or for that matter, whether the various releasing hormones may have functions other than mediating control of the pituitary by the brain.

Proliferation of receptors continues. It is likely that more than one type of receptor exists in the brain for most of the known neurotransmitters. Is it likely that specific receptors may be found for the very many centrally-acting drugs, such as seems to be the case for morphine, and that for each of these receptors for different types of drugs we may also expect to find an endogenous ligand? Does the finding of specific binding sites for benzodiazepines in the brain mean that God works for Hofmann-La Roche? Or does it simply mean that Artimitates Nature and that chlordiazepoxide is a weak imitator of Nature’s own antianxiety drug, which too often seems to be present in too low a quantity for many of our patients?

Thus, it is the basic sciences, as usual, that raise more questions than they answer. And here is where one of the major current problems lies. We must continue to try to make sense of old discoveries while adding confusion through new discoveries. The structure and function of the brain gets ever more complex, the more we know about it. Yet somewhere, there must be a synthesis that reduces the complexity. A biology that can code all the genetic information with four nucleotides, or make all the necessary proteins with a mere 20 amino acids, certainly does not require the anticipation of making receptors for every centrally acting drug that has been invented to date as well as those still to be invented. This problem is a never-ending one and is the reason that, for the true scientist, work never ceases to be a fascinating challenge.

From the viewpoint of the clinician, a major current problem is the development of better drugs than those that we have. The treatment of schizophrenia has improved immeasurably during the 20-year life span of the C.I.N.P., yet most improvements in antipsychotic drugs have been largely technical. Many current drugs are better than chlorpromazine, either due to more specific pharmacologic actions or by having fewer unwanted pharmacological actions. Yet, so far as we know, they still work in relatively similar ways. Our batteries of...