RESUMO
BACKGROUND: Positive allosteric modulators (PAMs) of the GABAB receptor constitute a new class of GABAB-receptor ligands. GABAB PAMs reproduce several pharmacological effects of the orthosteric GABAB receptor agonist, baclofen, although displaying a better safety profile. AIMS: This paper reviews the reducing or, frequently, even suppressing effects of all GABAB PAMs tested to date on multiple alcohol-related behaviours in laboratory rodents exposed to validated experimental models of human alcohol use disorder. RESULTS: Acute or repeated treatment with CGP7930, GS39783, BHF177, rac-BHFF, ADX71441, CMPPE, COR659, ASP8062, KK-92A, and ORM-27669 reduced excessive alcohol drinking, relapse- and binge-like drinking, operant alcohol self-administration, reinstatement of alcohol seeking, and alcohol-induced conditioned place preference in rats and mice. CONCLUSIONS: These effects closely mirrored those of baclofen; notably, they were associated to remarkably lower levels of tolerance and toxicity. The recent transition of ASP8062 to clinical testing will soon prove whether these highly consistent preclinical data translate to AUD patients.
Assuntos
Alcoolismo , Animais , Camundongos , Ratos , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Baclofeno/farmacologia , Baclofeno/uso terapêutico , Agonistas dos Receptores de GABA-B/farmacologia , Agonistas dos Receptores de GABA-B/uso terapêutico , Receptores de GABA-BRESUMO
Os inibidores da bomba de prótons (IBPs) são os fármacos mais utilizados no tratamento da doença do refluxo gastroesofágico (DRGE). Apesar de não reduzirem expressivamente o número de episódios de refluxo, propiciam mudança significativa na acidez. Isso quer dizer que continua havendo refluxo, porém os episódios são menos ácidos. Dessa forma consegue-se reduzir bastante os sintomas, sobretudo as queixas dependentes da acidez do material refluído.
Proton pump inhibitors (PPIs) are the most common medicine to treat gastroesophageal reflux disease (GERD). Although they don?t expressively reduce the amount of reflux episodes, it allows significantly changes in acidity. It means that reflux still exist, however, the episodes are less acid. As a result, symptoms can be reduced, mainly complaints due to acidity of the refluxed material.