engleski

FIFTY YEARS OF NEUROPSYCHOPHARMACOLOGY

In the fi fty years since the fi rst Pula congress a lot has changed in neuropsychopharmacology. Granted, the major groups of psychoactive drugs had already been discovered: neuroleptics, antidepressants, benzodiazepine anxiolitics, psychostimulants... Neurology was using the basic antiepileptics while, for example, the treatments for vascular and immunological diseases were more expectative. At the time of the fi rst Pula congress in 1960 we had only just discovered that myasthenia gravis is an autoimmune disease. It is also the year when dopamine defi ciency in the brain of Parkinsonian patients was discovered, a finding which was to revolutionize understanding and treatment of this disease. Th e last fi fty years have also seen a proliferation of approaches to therapy and the success of these medical fi elds has grown considerably. During this time, more than twenty researchers have been awarded the Nobel Prize for research related to functioning of the nervous system and have or will have a signifi cant infl uence on the development of new drugs. Th e greatest breakthroughs still waiting for clinical implementation have been in the fi eld of basic research. Discoveries of excitotoxicity mediated by glutamate receptors as well as neurogenesis in adults are creating brand new hypotheses on the pathophysiology of diff erent psychiatric and neurological diseases ranging from schizophrenia and drug abuse to ALS. However, speaking subjectively, there are two developments that had the deepest and strongest impact on pharmacology. First was the discovery of endogenous opioids based on the inquiry into real function of diff erent pharmacological receptors in our organism. Th is discovery has shown that the so-called pharmacological receptors did not evolve solely for the purpose of drug-deliverance but that they also have a physiological purpose in the functioning of an organism. Th e second important event was the discovery of methodology of reverse pharmacology – instead of a classic approach, nowadays receptors are more and more often synthesized from the human genome followed by search for their endogenous ligands and possibilities of their pharmacological manipulation. Th rough this, we now have orexines (hypocretins) as key neurotransmitters of wakefulness. By reverse pharmacology we have discovered such receptors as the new opioid receptor ORL1 and its endogenous ligand, nociceptin and fi nally, after several decades of diff erent assumptions, the prolactin-stimulating factor. What is especially intriguing and motivating is the fact that there are still hundreds of G-protein receptors, nuclear receptors and synaptic receptors waiting for researchers to discover their function and useful implementation through pharmacology.

neurofarmakologija; psihofarmakologija; povijest

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