title: Challenges for the pharmacological treatment of neurological and psychiatric disorders: Implications of the Ca(2+)/cAMP intracellular signalling interaction.
abstract: In 2013, we discovered that the entitled "calcium paradox" phenomenon, which means a paradoxical sympathetic hyperactivity produced by l-type Ca(2+) channel blockers (CCBs), used in antihypertensive therapy, is due to interaction between the intracellular signalling pathways mediated by Ca(2+) and cAMP (Ca(2+)/cAMP interaction). In 2015, we proposed that the pharmacological manipulation of this interaction could be a new therapeutic strategy for increasing neurotransmission in psychiatric disorders, and producing neuroprotection in the neurodegenerative diseases. Besides the paradoxical sympathetic hyperactivity produced by CCBs, several clinical studies have been demonstrating pleiotropic effects of CCBs, including neuroprotective effects. CCBs genuinely exhibit cognitive-enhancing abilities and reduce the risk of dementia, including Alzheimer's, Parkinson´s disease and others. The molecular mechanisms involved in these pleiotropic effects remain under debate. Our recent discovery that the "calcium paradox" phenomenon is due to Ca(2+)/cAMP interaction may provide new insights for the pharmacological treatment of neurological and psychiatric disorders, including enhancement of current therapies mainly by reducing adverse effects, and improving effectiveness of modern medicines. Whether Ca(2+)/cAMP interaction is involved in CCBs pleiotropic effects also deserves special attention. Then, the pharmacological manipulation of the Ca(2+)/cAMP interaction could be a more efficient therapeutic strategy for increasing neurotransmission in psychiatric disorders, and producing neuroprotection in the neurodegenerative diseases. Thus, in this review we summarize the current knowledge of this field, making new directions and future perspectives.
authors.affiliation: Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, Laboratory of Autonomic and Cardiovascular Pharmacology, 55 11 5576-4973, Rua Pedro de Toledo, 669, Vila Clementino, São Paulo, SP CEP 04039-032, Brazil. Electronic address: leanbio39@yahoo.com.br.
authors.forename: Leandro Bueno
authors.initials: LB
authors.lastname: Bergantin
authors.affiliation: Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, Laboratory of Autonomic and Cardiovascular Pharmacology, 55 11 5576-4973, Rua Pedro de Toledo, 669, Vila Clementino, São Paulo, SP CEP 04039-032, Brazil.
authors.forename: Afonso
authors.initials: A
authors.lastname: Caricati-Neto
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000473:pathology; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000242:Cyclic AMP; D002118:Calcium
keywords: Ca(2+)/cAMP signalling interaction; Neurological and psychiatric disorders