RESUMO
Prospect Theory (PT) is an alternative, dynamic explanation of the phenomenon of risky decision making. This research presents an overview of PT's history in health fields, including advancements, limitations, and bibliometric data. A systematic and bibliometric review of the scientific literature included in the psychological categories of Web of Science (WoS) was performed following the PRISMA 2020 statement for systematic reviews. A total of 37 studies (10 non-empirical and 27 empirical) were included in the sample. Bibliometric results showed thematic variability and heterogeneity regarding the production, researchers, and methodologies that are used to study PT. The systematic results highlight three main fields of PT research: preventive and screening behaviors, promotion of healthy habits, and COVID-related decision making. Personal and contextual factors which alter the usual pattern specified by PT are also described. To conclude, PT currently has an interdisciplinary character suitable for health promotion, with recent studies broadening its applicability.
RESUMO
The potential therapeutic use of some Cannabis sativa plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of efficacy of the current treatments. Numerous studies have been carried out using the main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD displays an interesting pharmacological profile without the potential for becoming a drug of abuse, unlike THC. In this review, we focused on the anxiolytic, antidepressant, and antipsychotic effects of CBD found in animal and human studies. In rodents, results suggest that the effects of CBD depend on the dose, the strain, the administration time course (acute vs. chronic), and the route of administration. In addition, certain key targets have been related with these CBD pharmacological actions, including cannabinoid receptors (CB1r and CB2r), 5-HT1A receptor and neurogenesis factors. Preliminary clinical trials also support the efficacy of CBD as an anxiolytic, antipsychotic, and antidepressant, and more importantly, a positive risk-benefit profile. These promising results support the development of large-scale studies to further evaluate CBD as a potential new drug for the treatment of these psychiatric disorders.
Assuntos
Ansiedade/tratamento farmacológico , Canabidiol/administração & dosagem , Depressão/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Animais , Ansiedade/metabolismo , Ansiedade/psicologia , Canabidiol/metabolismo , Depressão/metabolismo , Depressão/psicologia , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Humanos , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/psicologia , Resultado do TratamentoRESUMO
α7 Nicotinic acetylcholine receptors (nAChRs) are ion channels implicated in a number of CNS pathological processes, including pain and psychiatric, cognitive and inflammatory diseases. Comparing with orthosteric agonism, positive allosteric modulation of these channels constitutes an interesting approach to achieve selectivity versus other nicotinic receptors. We have recently described new chalcones and 1,3-diphenylpropanones as positive allosteric modulators (PAMs) of α7 nAChRs, which proved to have good analgesic activities but poor pharmacokinetic properties. Here we report the preparation of amino acid and peptide derivatives as prodrugs of these modulators with the aim of improving their in vivo biological activity. While the valine derivative showed very short half life in aqueous solutions to be considered a prodrug, Val-Val and Val-Pro-Val are suitable precursors of the parent 1,3-diphenylpropanones, via chemical and enzymatic transformation, respectively. Compounds 19 (Val-Val) and 21 (Val-Pro-Val), prodrugs of the 2',5',4-trihydroxy-1,3-diphenylpropan-1-one 3, showed significant antinociceptive activity in in vivo assays. The best compound, 21, displayed a better profile in the analgesia test than its parent compound 3, exhibiting about the same potency but long-lasting effects.
Assuntos
Aminoácidos/farmacologia , Analgésicos/farmacologia , Dor/tratamento farmacológico , Peptídeos/farmacologia , Fenilpropionatos/farmacologia , Pró-Fármacos/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Regulação Alostérica/efeitos dos fármacos , Aminoácidos/síntese química , Aminoácidos/química , Analgésicos/síntese química , Analgésicos/química , Animais , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Adjuvante de Freund , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Estrutura Molecular , Medição da Dor , Peptídeos/síntese química , Peptídeos/química , Fenilpropionatos/síntese química , Fenilpropionatos/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade , XenopusRESUMO
We have studied the role of different amino acids in the M2 transmembrane domain of the α7 neuronal nicotinic receptor by mutating residues that differ from the ones located at the same positions in other α (α2-α10) or ß (ß2-ß4) subunits. Our aim was to investigate the contribution of these amino acids to the peculiar kinetic and inward rectification properties that differentiate the homomeric α7 receptor from other nicotinic receptors. Mutations of several residues strongly modified receptor function. We found that Thr245 had the most profound effect when mutated to serine, an amino acid present in all heteromeric receptors composed of α and ß subunits, by dramatically increasing the maximal current, decreasing the decaying rate of the currents and decreasing receptor rectification. Some mutants also showed altered agonist-binding properties as revealed by shifts in the dose-response curves for acetylcholine. We conclude that residues in the M2 segment and flanking regions contribute to the unusual properties of the α7 receptor, especially to its characteristic fast kinetic behavior and strong inward rectification and furthermore to the potency of agonists.
Assuntos
Ativação do Canal Iônico/fisiologia , Receptores Nicotínicos/metabolismo , Acetilcolina/metabolismo , Algoritmos , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Bungarotoxinas/metabolismo , Bovinos , DNA Complementar/biossíntese , DNA Complementar/genética , Fenômenos Eletrofisiológicos , Ativação do Canal Iônico/genética , Cinética , Potenciais da Membrana/fisiologia , Modelos Moleculares , Dados de Sequência Molecular , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Técnicas de Patch-Clamp , Ligação Proteica , Receptor Muscarínico M2/efeitos dos fármacos , Receptor Muscarínico M2/metabolismo , Receptores Nicotínicos/genética , Xenopus laevis , Receptor Nicotínico de Acetilcolina alfa7RESUMO
Using a yeast two-hybrid screening we report the isolation of a novel human protein, hCRELD2beta, that interacts specifically with the large cytoplasmic regions of human nicotinic acetylcholine receptor (nAChR) alpha4 and beta2 subunits, both in yeast cells and in vitro. This interaction is not detected with nAChR alpha7 and alpha3 subunits. The hCRELD2 gene encodes for multiple transcripts, likely to produce multiple protein isoforms. A previously reported one has been renamed as CRELD2alpha. Isoforms alpha and beta are expressed in all tissues examined and have the same N-terminal and central regions but alternative C-terminal regions. Both isoforms interact with the alpha4 subunit. Within this subunit the interaction was localized to the N-terminal region of the large cytoplasmic loop. The CRELD2beta protein is present at the endoplasmic reticulum where colocalized with alpha4beta2 nAChRs upon cell transfection. Immunohistochemistry experiments demonstrated the presence of CRELD2 in the rat brain at sites where alpha4beta2 receptors have been previously detected. Labeling was restricted to neuronal perikarya. Finally, CRELD2 decreases the functional expression and impairs membrane transport of alpha4beta2 nAChRs in Xenopus leavis oocytes, without affecting alpha3beta4 and alpha7 nAChR expression. These results suggest that CRELD2 can act as a specific regulator of alpha4beta2 nAChR expression.
Assuntos
Moléculas de Adesão Celular/metabolismo , Cisteína/fisiologia , Citoplasma/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Neurônios/metabolismo , Receptores Nicotínicos/metabolismo , Sequência de Aminoácidos , Northern Blotting , Western Blotting , Química Encefálica/fisiologia , Células Cultivadas , DNA Complementar/biossíntese , DNA Complementar/genética , DNA Recombinante/biossíntese , DNA Recombinante/genética , Retículo Endoplasmático/metabolismo , Biblioteca Gênica , Humanos , Imuno-Histoquímica , Microscopia Confocal , Dados de Sequência Molecular , Plasmídeos/genética , Dobramento de Proteína , Frações Subcelulares/metabolismo , Transfecção , Leveduras/genética , beta-Galactosidase/metabolismoRESUMO
Ginseng saponins, major active components of ginseng root used by folk medicine in the treatment of various diseases, produce multiple pharmacological responses having many effects on the central and peripheral nervous system. Specifically, ginsenoside Rg(2) has been shown to block the nicotinic acetylcholine receptors in bovine chromaffin cells. We have studied the effect of Rg(2) on different types of human neuronal nicotinic acetylcholine receptors (nAChRs), both homomeric and heteromeric, expressed in Xenopus oocytes. Rg(2) did not affect the acetylcholine (ACh)-induced currents in alpha(7) human receptors, however Rg(2) affected the peak currents, and mainly the desensitization of heteromeric receptors alpha(3)beta(4), alpha(3)beta(2), alpha(4)beta(4), and alpha(4)beta(2). Both effects, a diminution of peak current and an increase of desensitization, are dose-dependent and are very similar for all the receptors. The mechanism of action has been studied in more detail in alpha(3)beta(4) and alpha(4)beta(2) receptors where we found a negligible shift in the ACh dose-response curves and a persistence of the Rg(2) effects at high ACh concentrations, indicative of a noncompetitive antagonism. A lack of voltage dependence on the reduction of the peak currents induced by ACh also suggests that Rg(2) does not act as an open channel blocker of human nAChR. The results indicate that Rg(2) acts specifically on heteromeric human nAChRs modulating their desensitization and suggest a possible mechanism by which this saponin contributes to the multiple therapeutic effects of ginseng.
Assuntos
Ginsenosídeos , Panax/química , Receptores Nicotínicos/metabolismo , Saponinas/farmacologia , Animais , Relação Dose-Resposta a Droga , Vetores Genéticos/antagonistas & inibidores , Vetores Genéticos/metabolismo , Humanos , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Técnicas de Patch-Clamp , Receptores Nicotínicos/fisiologia , Saponinas/química , Transfecção , Xenopus/genéticaRESUMO
We investigated the effects of ginsenosides, the active ingredient of ginseng, on neuronal or muscle-type nicotinic acetylcholine receptor channel activity expressed in Xenopus oocytes after injection of cRNA encoding bovine neuronal alpha3beta4, alpha7 or human muscle alphabetadeltavarepsilon subunits. Treatment with acetylcholine elicited an inward peak current (I(ACh)) in oocytes expressing nicotinic acetylcholine receptor subtypes. Cotreatment with ginsenoside Rg2 and acetylcholine inhibited I(ACh) in oocytes expressing with alpha3beta4 or alphabetadeltavarepsilon but not in oocytes expressing alpha7 nicotinic acetylcholine receptors. The inhibition of I(ACh) by ginsenoside Rg2 was reversible and dose-dependent. The half-inhibitory concentrations (IC50) of ginsenoside Rg2 were 60.2+/-14.1 and 15.7+/-3.5 microM in oocytes expressing alpha3beta4 and alphabetadeltavarepsilon nicotinic acetylcholine receptors, respectively. The inhibition of I(ACh) by ginsenoside Rg2 was voltage-independent and noncompetitive. Other ginsenosides besides ginsenoside Rg2 also inhibited I(ACh) in oocytes expressing alpha3beta4 or alphabetadeltavarepsilon nicotinic acetylcholine receptors. The order of potency for the inhibition of I(ACh) was ginsenoside Rg2>Rf>Re>Rg1>Rc>Rb2>Rb1 in oocytes expressing alpha3beta4 nicotinic acetylcholine receptors and was ginsenoside Rg2>Rf>Rg1>Re>Rb1>Rc>Rb2 in oocytes expressing alphabetadeltavarepsilon nicotinic acetylcholine receptors. These results indicate that ginsenosides might regulate nicotinic acetylcholine receptors in a differential manner and this regulation might be one of the pharmacological actions of Panax ginseng.