Department of Applied Pharmacy, Medical University of Lublin, Lublin, Poland.
Department of Pharmacokinetics and Physical Pharmacy, Collegium Medicum, Jagiellonian University, Kraków, Poland.
J Pharm Pharmacol. 2018 Sep;70(9):1200-1208. doi: 10.1111/jphp.12954. Epub 2018 Jun 25.
The main goal of our study was to investigate whether a selective antagonism of the adenosine A or A receptors is able to enhance the antidepressant activity of commonly prescribed drugs.
All experiments were carried out on male Albino Swiss mice. The forced swim test and the tail suspension test were used to evaluate the antidepressant-like potential. Drug concentrations in animals' serum and brains were measured by high-performance liquid chromatography.
The antidepressant potential of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg) and bupropion (10 mg/kg) was enhanced by a co-administration with 3,7-dimethyl-1-propargylxanthine (DMPX; an antagonist of adenosine A receptors; 3 mg/kg) or 8-cyclopentyl-1,3-dipropylxanthine (an antagonist of adenosine A receptors; 1 mg/kg). However, significant interactions between the tested substances were detected only in the experiments with DMPX. The nature of the observed interplays is rather pharmacodynamic than pharmacokinetic, because neither serum nor brain concentrations of the used drugs were significantly increased.
Blockage of the adenosine receptors (particularly the A subtypes) could be considered in future as a novel, promising part of the combined antidepressant therapy. However, further studies on this subject are needed.
我们研究的主要目的是探究腺苷 A1 或 A2A 受体的选择性拮抗作用是否能够增强常用药物的抗抑郁活性。
所有实验均在雄性白化瑞士小鼠上进行。使用强迫游泳试验和悬尾试验评估抗抑郁样潜能。通过高效液相色谱法测量动物血清和脑中的药物浓度。
吗氯贝胺（1.5mg/kg）、文拉法辛（1mg/kg）和安非他酮（10mg/kg）的抗抑郁潜能通过与 3,7-二甲基-1-丙炔基黄嘌呤（DMPX；腺苷 A 受体拮抗剂；3mg/kg）或 8-环戊基-1,3-二丙基黄嘌呤（腺苷 A 受体拮抗剂；1mg/kg）联合给药而增强。然而，仅在使用 DMPX 的实验中检测到测试物质之间的显著相互作用。观察到的相互作用的性质更倾向于药效学而不是药代动力学，因为所用药物的血清和脑浓度均未显著增加。
阻断腺苷受体（特别是 A2A 亚型）可被视为联合抗抑郁治疗的一种新的、有前途的方法。然而，还需要对此主题进行进一步研究。
