• The Korean Journal of Pain
• /
• 제35권1호
• /
• pp.59-65
• /
• 2022

Background: There is still unmet need in treating neuropathic pain and increasing awareness regarding the use of drug combinations to increase the effectiveness of treatment and reduce adverse effects in patients with neuropathic pain. Methods: This study was performed to determine the individual and combined effects of pregabalin, tianeptine, and clopidogrel in a rat model of neuropathic pain. The model was created by ligation of the L5-L6 spinal nerve in male Sprague-Dawley rats; mechanical allodynia was confirmed using von Frey filaments. Drugs were administered to the intrathecal space and mechanical allodynia was assessed; drug interactions were estimated by isobolographic or fixed-dose analyses. Results: Intrathecal pregabalin and tianeptine increased the mechanical withdrawal threshold in a dose-dependent manner, but intrathecal clopidogrel had little effect on the mechanical withdrawal threshold. An additive effect was noted between pregabalin and tianeptine, but not between pregabalin and clopidogrel. Conclusions: These findings suggest that intrathecal coadministration of pregabalin and tianeptine effectively attenuated mechanical allodynia in the rat model of neuropathic pain. Thus, pregabalin plus tianeptine may be a valid option to enhance the efficacy of neuropathic pain treatment.

• The Korean Journal of Physiology and Pharmacology
• /
• 제21권4호
• /
• pp.361-370
• /
• 2017

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

• 한국산학기술학회논문지
• /
• 제13권5호
• /
• pp.2125-2132
• /
• 2012

Fluoxetine과 tianeptine은 보편적으로 사용되는 항우울제 (AD)이며, haloperidol과 risperidone도 많이 사용되는 항정신성 (APD) 약물로 다양한 이온채널을 조절한다. TREK2 채널은 우울증과 정신분열증 같은 정신질환에 대한 병태생리학적으로 중요한 역할을 하는 TREK1 채널과 생리학적 성질이 매우 비슷하여, 정신성 및 우울증 약물의 TREK2 채널에 대한 효과가 TREK1과 유사하게 나타날 가능성이 있다. Excised inside-out 팻취 방법을 사용하여, 클론된 TREK2 채널이 발현된 CHO 세포에서 항정신성 약물과 항우울제의 효과를 조사했다. Fluoxetine (선택적 세로토닌 방출 억제제, SSRI)은 TREK2 채널을 농도 의존적으로 억제하였으나 ($IC_{50}=13{\mu}M$), tianeptine (선택적 세로토닌 재흡수 증가제, SSRE)은 TREK2 채널 활성을 감소시키지 않고 증가시켰다. Haloperidol은 TREK2 채널을 농도 의존적으로 억제하였으나 ($IC_{50}=44{\mu}M$), risperidone은 고농도 ($100{\mu}M$)에서도 TREK2 채널 활성을 완전히 억제 시키지 못했다. 본 연구는 tianeptine 보다 fluoxetine이 TREK2 채널을 더 잘 억제하고 risperidone 보다 haloperidol에 더 잘 억제됨을 보여 주었고, TREK2 채널에 대한 항정신성 약물과 항우울제의 차별적 작용이 약물 부작용의 어떤 기전에 기여 할 수 있음을 제시한다.

• 생물정신의학
• /
• 제6권1호
• /
• pp.34-40
• /
• 1999

New antidepressants have become available for clinical use in the 1990s. Before this decade, the drugs available to treat depression consisted essentially of monoamine oxidase inhibitors, tricyclic antidepressants, and lithium. Following the introduction of SSRIs, the options have expanded and now include SSRIs, nefazodone, venlafaxine, mirtazapine, reboxetine, tianeptine. Newer antidepressants possess a variety of pharmacological characteristics that are relevant to the choice of an antidepressant for clinical use. This review summarizes some of the major pharmacological characteristics among the drugs.