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Possible role of adenosine receptors in psychiatric diseases
Author(s) -
van Calker Dietrich,
Berger Mathias
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280330
Subject(s) - adenosine , inositol , neurotransmitter , receptor , synaptic plasticity , neuroscience , pharmacology , neurotransmitter receptor , chemistry , lithium (medication) , carbamazepine , long term potentiation , 5 ht2 receptor , medicine , endocrinology , psychology , 5 ht receptor , biology , serotonin , biochemistry , epilepsy
Effective antidepressive treatments like electroconvulsive therapy and sleep deprivation increase adenosine A 1 ‐receptors in the brains of experimental animals. It has therefore been of considerable interest that carbamazepine, which is known to be clinically similarly effective as lithium ions in the prophylaxis of affective illness, interacts with adenosine receptors. We have recently characterized this interaction using cellular model systems, in which adenosine receptor subtypes evoke different second messenger responses. The results show that carbamazepine at therapeutically relevant concentrations, is a selective antagonist of the A 1 ‐ but not of the high affinity A 2 ‐receptor subtype. The increase in the frequency and severity of the episodes that is often observed in the course of affective illness has been interpreted as the result of plastic changes in neuronal sensitivity that lead to the development of pathologically supersensitive neural circuits. The prophylactic properties of lithium ions are thought to be due to a dampening of the inositol‐phospholipid second not directly influence the generation of inositol phosphates. However, adenosine‐agonists, presumably acting via A 1 ‐receptors, can potently modulate the neurotransmitter‐evoked increase of inositol phosphates and cytosolic free calcium ions. This effect could play a role in synaptic plasticity. Indeed, A 1 ‐agonists can block the development of “long term potentiation,” a model of synaptic plasticity. We suggest that the prophylactic properties of carbamazepine in affective psychoses might be related to the inhibition by carbamazepine and the subsequent supersensitization of the A 1 ‐receptors that modulate the neurotransmitter‐induced formation of inositol phosphates and synaptic plasticity. © 1993 Wiley‐Liss, Inc.