• 약학회지
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• 제29권4호
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• pp.165-175
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• 1985

It has been reported that clonidine is $\alpha_2$-adrenergic agonist, potnet new hypotensive drug in human with low dose. The change in blood pressure is implicated in the concentration, release, uptake and metabalism of catecholamine and activity of catecholamine synthesizing enzyme in specific brain areas. Thus the experiment was set up to investigate the effect on the enzyme activity of clonidine alone and that of clonidine pretreated with imipramine or tranylcypromine by measuring activity of the Dopa-forming enzyme, tyrosine hydroxylase (TH) and epinephrine forming enzyme, phenylethanolamine-N-methyl transferase (PNMT) in brain and adrenal gland. The TH activity in brainstem and substantia nigra is decreased by intraperitoneally administered clonidine 0.1mg/kg twice a day for 5 days, but increased in the rats pretreated with imipramine 10mg/kg intraperitoneally given 26 hrs and 5 hrs before decaptitation. However the TH activity in all regions of brain is increased in rats pretreated with tranylcypromine 10mg/kg intraperitoneally twice a day for 5 days. The effect of clonidine on TH activity is due to inhibition release of norepinephrine by activation of presynaptic $\alpha_2$-adrenoreceptor, axon terminal result in the decrease of TH activity in brain. The increasing of TH activity in brain results in attenuation of the role of clonidine by pretreated with imipramine or tranylcypromine in rats. The activity of PNMT was not significantly affected by clonidine, imipramine and tranylcypromine in adrenal gland.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.230-239
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• 2020

Previous studies have shown disrupted synaptic plasticity and neural activity in depression. Such alteration is strongly associated with disrupted synaptic structures. Chronic stress has been known to induce changes in dendritic structure in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), but antidepressant effect on structure of these brain areas has been unclear. Here, the effects of imipramine on dendritic spine density and morphology in BLA and mPFC subregions of stressed mice were examined. Chronic restraint stress caused depressive-like behaviors such as enhanced social avoidance and despair level coincident with differential changes in dendritic spine structure. Chronic stress enhanced dendritic spine density in the lateral nucleus of BLA with no significant change in the basal nucleus of BLA, and altered the proportion of stubby or mushroom spines in both subregions. Conversely, in the apical and basal mPFC, chronic stress caused a significant reduction in spine density. The proportion of stubby or mushroom spines in these subregions overall reduced while the proportion of thin spines increased after repeated stress. Interestingly, most of these structural alterations by chronic stress were reversed by imipramine. In addition, structural changes caused by stress and blocking the changes by imipramine were corelated well with altered activation and expression of synaptic plasticity-promoting molecules such as phospho-CREB, phospho-CAMKII, and PSD-95. Collectively, our data suggest that imipramine modulates stress-induced changes in synaptic structure and synaptic plasticity-promoting molecules in a coordinated manner although structural and molecular alterations induced by stress are distinct in the BLA and mPFC.

• BMB Reports
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• 제44권10호
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• pp.647-652
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• 2011

The protein transduction domains have been reported to have potential to deliver the exogenous molecules, including proteins, to living cells. However, poor transduction of proteins limits therapeutic application. In this study, we examined whether imipramine could stimulate the transduction efficiency of PEP-1 fused proteins into astrocytes. PEP-1-catalase (PEP-1-CAT) was transduced into astrocytes in a time- and dose-dependent manner, reducing cellular toxicity induced by $H_2O_2$. Additionally, the group of PEP-1-CAT + imipramine showed enhancement of transduction efficiency and therefore increased cellular viability than that of PEP-1-CAT alone. In the gerbil ischemia models, PEP-1-CAT displayed significant neuroprotection in the CA1 region of the hippocampus. Interestingly, PEP-1-CAT + imipramine prevented neuronal cell death and lipid peroxidation more markedly than PEP-1-CAT alone. Therefore, our results suggest that imipramine can be used as a drug to enhance the transduction of PEP-1 fusion proteins to cells or animals and their efficacies against various disorders.

• Clinical and Experimental Pediatrics
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• 제51권11호
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• pp.1232-1235
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• 2008

삼환계 항우울제의 하나인 이미프라민은 우울장애와 야뇨증, 불안장애, 신경성 통증에 쓰인다. 그러나 이미프라민을 포함한 삼환계 항우울제는 많은 부작용이 관찰되는 데, 항콜린성 작용으로 초기에 입이 마르고 동공산대, 소변 정체, 동성빈맥을 보인다. 또한 중추신경계에 작용하여 섬망, 불안, 초조, 환각, 경련, 혼수를 야기할 수 있다. 그러나 앞에서 말한 부작용 보다도 치명적인 것인 삼환계 항우울제에 의해 소디움 채널 차단으로 인한 부정맥이다. QRS파의 연장과 QTc 연장, 넓은 QRS파 빈맥, Brugada 심전도 양상이 나타나며 이런 현상은 중탄산 나트륨을 통해 나트륨을 대량으로 공급하여 회복시킬 수 있다. 이미프라민을 포함한 삼환계 항우울제에는 아직도 널리 쓰이고 있지만 지금까지 소아에서 부정맥이 부작용으로 나타난 증례에 대한 보고가 없었다. 따라서 저자들은 이미프라민 과량복용 후 경련, 넓은 QRS파를 보이는 빈맥, Brugada 심전도 양상, 무뇨를 보인 환아를 경험, 치료하여 이를 보고한다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제5권1호
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• pp.93-101
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• 1994

반복적으로 공격적인 행동 양상을 보이는 사람들의 세로토닌 반응(serotonergic responsivity)이 정상인과 비교하여 차이가 있을 것인지를 알아보고자 연구를 실시하였다. 나이를 대조하여 공격성군(소년원 재소자 16명)과 대조군(의과대학생 17명)으로 구분한 연구대상에게, 여러 심리검사 척도를 이용하여 공격성의 심한 정도를 정의하고, 두뇌의 세로토닌 기능과 일치하는 것으로 알려진 혈소판의 이미프라민 결합을 측정하여 다음과 같은 결과를 얻었다. 1) 공격성군은 대조군에 비하여 공격척도상 신체적 공격성(physical aggression)의 평균이 모두 유의하게 높은 값을 나타내었다. 이외에도 공격성군은 대조군에 비해 충동성(impulsivity), 적대감(hostility), 정신증(psychoticism)등이 통계적으로 유의하게 높은 평균값을 보였다. 2) 공격성군은 대조군에 비하여 혈소판 이미프라민 최대결합부위 밀도(Bmax)가 낮은 경향을 보였다. 3) 공격성군과 대조군의 혈소판 이미프라민 결합의 결합상수(Kd) 값은 통계적으로 유의한 차이를 보이지 않았다. 4) 연구대상군을 전체로 하였을 때, 공격성척도(PFAV)와 갈등해결 척도(CTS)의 신체적 공격성의 심한 정도는 혈소판 이미프라민 최대결합부위 밀도(Bmax)와 통계적으로 유의한 정도의 역비례 상관관계를 보였다.

• 대한수의학회지
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• 제43권4호
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• pp.597-606
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• 2003

Although the antidepressant effects of imipramine (IMI) have been well known in several studies, the effects on cardiovascular system, particularly the vasorelaxant effects, have not known clearly. We hypothesis that IMI-induced vasorelaxation involves NO (nitrie oxide), activation of guanylate cyclase (GC) and $Ca^{2+}$ channel. The possible roles of the endothelium and $Ca^{2+}$ in IMI-induced responses were investigated using isolated rings of rat thoracic aorta and anesthesized rats. In KCl-precontracted rings. IMI produces endothelium-dependent and endothelium-independent relaxations in intact (+E) as well as endothelium-denuded (-E) rat aorta in a concentration-dependent manner. In phenylephrine (PE)-precontracted rings, the IMI-induced relaxation was significantly greater in +E rings. The IMI-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, a non-selective GC inhibitor, methylene blue, $Na^+$ channel blockers, lidocaine and procaine, or $Ca^{2+}$ channel blockers, nifedipine and verapamil, in PE-precontracted +E rings, but not in PE-precontracted -E rings. These relaxations were also suppressed by lidocaine or procaine in -E aortic rings. However, IMI-induced relaxations were not inhibited by a PLC inhibitor 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC), an inositol monophosphatase inhibitor, lithium, indomethacin and dexamethasone in +E and -E rings. In vivo, infusion of IMI elicited significant decrease in arterial blood pressure. After intravenous injection of saponin, NOS inhibitors. MB and nifedipine, infusion of IMI inhibited the IMI-lowered blood pressure markedly. These findings suggest that the endothelium-dependent relaxation induced by IMI is mediated by activation of NO/cGMP signaling cascade or inhibition of $Ca^{2+}$ entry through voltage-gated channel, and this mechanism may contribute to the hypotensive effects of IMI in rats.

• Journal of Yeungnam Medical Science
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• 제32권2호
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• pp.85-89
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• 2015

Background: We examined the usefulness of urine osmolality, as a predictive factor in the treatment of monosymptomatic nocturnal enuresis (NE) with combination therapy of imipramine and desmopressin. Methods: From May 2014 to April 2015, 59 monosymptomatic NE patients participated in this study. Early morning urine osmolality was measured at 1 week and 1 day before combination therapy of imipramine and desmopressin, and at 1 week and 2 weeks after therapy. The response to combination therapy was evaluated at 3 months after treatment. The mean period of combination therapy was $6.4{\pm}4.2weeks$. Therapeutic response was classified as complete (0-1 wet night/week), partial (over 50% reduction of night) and non-responders (less than 50% reduction of night). Results: The cumulative rate of the complete and partial responders was 76.3%. Among the 3 groups, the statistically lowest value of pre-treatment urine osmolality was observed in the complete responder group (p<0.001). Urine osmolality increased in all groups after treatment, however, statistically the greatest difference between pre and post-treatment urine osmolality was observed in the complete responder group (p=0.024). No serious side effects were observed. Conclusion: Early morning urine osmolality and change of urine osmolality between pre and post-treatment have predictive values in the response to combined imipramine and desmopressin for treatment of monosymptomatic NE.

• Archives of Pharmacal Research
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• 제12권4호
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• pp.282-288
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• 1989

This study was investigated the effects of imipramine (IMI) and electroconvulsive shock (ECS), which are used as antidepressant therapy, on the central $\beta_1$or $\beta_2$ adrenergic receptor in anesthetized rats. The resting blood pressure and heart rate decreased in reserpinized group (5 mg/kg i. p., 24 hr before), but not in order 4 groups i. e. acute IMI (20 mg/kg i. p.. 3-5 hr before), chronic IMI (Same dose, twice a day for 14 days), siggle ECS (sinusoidal 20 Hz, 120 V for 2 sec) and repeated ECS (same condition, daily for 12 days). The increase of heart rate and hypotension evoked by 1 or 3 $\mu$g intracerebroventricular (i. c. v.) administration of (+) dobutamine, $\beta_2$-agonist, 1 or 3 $\mu$g i. c. v. was significantly attenuated in repeated ECS or reserpine treatment. And, the diminuation of pulse pressure of salbutamol also reduced by repeated ECS. These results suggest that IMI or ECS result in attenuation on tachycardia by (+) dobutamine or on hypotension by salbutamol, presumably by which the central $\beta_1$ or $\beta_2$receptor sensitivity may be suppressed, repectively.

• 운동영양학회지
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• 제23권2호
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• pp.1-6
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• 2019

[Purpose] Strenuous exercise often induces skeletal muscle damage, which results in impaired performance. Sphingolipid metabolism contributes to various cellular processes, including apoptosis, stress response, and inflammation. However, the relationship between exercise-induced muscle damage and ceramide (a key component of sphingolipid metabolism), is rarely studied. The present study aimed to explore the regulatory role of sphingolipid metabolism in exercise-induced muscle damage. [Methods] Mice were subjected to strenuous exercise by treadmill running with gradual increase in intensity. The blood and gastrocnemius muscles (white and red portion) were collected immediately after and 24 h post exercise. For 3 days, imipramine was intraperitoneally injected 1 h prior to treadmill running. [Results] Interleukin 6 (IL-6) and serum creatine kinase (CK) levels were enhanced immediately after and 24 h post exercise (relative to those of resting), respectively. Acidic sphingomyelinase (A-SMase) protein expression in gastrocnemius muscles was significantly augmented by exercise, unlike, serine palmitoyltransferase-1 (SPT-1) and neutral sphingomyelinase (N-SMase) expressions. Furthermore, imipramine (a selective A-SMase inhibitor) treatment reduced the exercise-induced CK and IL-6 elevations, along with a decrease in cleaved caspase-3 (Cas-3) of gastrocnemius muscles. [Conclusion] We found the crucial role of A-SMase in exercise-induced muscle damage.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제3권1호
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• pp.26-45
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• 1992

본 연구는 약물의 작용기전이 각기 다른 methylphenidate와 imipramine을 투여하여 주의력결핍(注意力缺乏)${\cdot}$과잉운동장애(過剩運動障碍)(attention deficit-hyperactivity disorder : ADHD)아동에서 부모와 교사의 평정척도(平定尺度)로 행동변화를 그리고 신경심리학적검사(神經心理學的檢査)로 주의력(注意力)과 인지기능(認知機能)을 측정하여 두 약물이주는 영향이 행동영역(行動領域)과 인지기능(認知機能)에서 어떻게 다르게 나타나는 지를 비교검토해 본 것이다. 저자들은 미국정신의학회 정신질환 진단기준편람 개정3판(DSM-III-R)에 의거하여 주의력결핍(注意力缺乏)${\cdot}$과잉운동장애(過剩運動障碍)로 진단받은 생후 만 5년 6개월부터 12년 1개월사이의 남아 30명을 대상으로 이들의 임상적${\cdot}$의학적 특성을 조사하고, 지능검사를 포함한 신경심리학적검사(神經心理學的檢査)를 시행한 뒤, 부모(父母) 및 교사용(敎師用) 평정척도(評定尺度)로 이들의 행동을 평가하였다. 그리고 평가된 아동을 무작위로 15명씩 두 집단으로 나누어 각각 methylphenidate($0.5{\sim}0.6mg/kg)$와 imipramine(25${\sim}100mg$)을 경구투여(經口投與)하고, 투여 1개월후 및 2개월후에 각 1회씩 다시 부모와 교사들에게 같은 평정척도(評定尺度)로 이들의 행동을 평가시키고 아울러 지능검사(知能檢査)를 제외한 모든 신경심리학적검사(神經心理學的檢査)를 시행하였다. 그 결과를 보면 imipramine을 투여받은 아동들은 투여 1개월후 아동행동조사표(兒童行動調査表)(CBCL)의 외상성(外商性)과 과잉행동(過剩行動)${\cdot}$사회적위축요인(社會的萎縮要因)에서 호전을, 그리고 2개월후에는 학교상황질간지(學校狀況質間紙), 코너스씨(氏) 단축형 교사평정척도(短縮形 敎師平定尺度)(CATRS) 및 연속과제수행(連續課題遂行)(CPT)에서 호전을 보였다. 반면 methylphenidate를 투여받은 아동들은 투여 1개월후 부터 부모가 평가하는 코너스씨(氏) 단축형 부모평정척도(短縮形 父母平定尺度)(CAPRS), 아동행동조사표(兒童行動調査表) 및 연속과제수행(連續課題遂行)에서 호전을 보였고, 투여 2개월후에서도 같은 양상의 호전을 보였으며, 또한 아동행동조사표(兒童行動調査表)에서 외향성(外向性)은 물론 소통불능(疏通不能)${\cdot}$사회적위축(社會的萎縮)${\cdot}$과잉행동(過剩行動)${\cdot}$공격성(攻擊性)${\cdot}$비행요인(非行要因)에서도 호전양상을 보였다. 이와같은 결과는 이 두 약물이 모두 주의력(注意力)과 인지기능(認知機能)을 증진시키기는 하였으나, 보다 뚜렷한 변화는 methylphenidate 투여후에 볼 수 있었다. 특히 methylphenidate투여후 연속과제수행(連續課題遂行)에서 민감도(敏感度)와 반응오류수(反應誤謬數)의 호전이 있었으나 반응기준(反應基準)에는 변화가 없었다는 소견, 그리고 단기기억수행(短期記憶遂行)에서의 호전과 '같은 그림 찾기' 검사의 오류수(誤謬數)에서 변화가 없었다는 소견은 methylphenidate가 훈기요인(勳機要因)의 호전에 의한 이차적인 변화에 의한 것이 아니라 주의집중력(注意集中力)에 직접적으로 효과를 나타내는 것으로 해석할 수 있었다. 또한 이같은 소견으로 주의력결핍(注意力缺乏)${\cdot}$과잉운동장애환아(過剩運動障碍患兒)에서의 충동성(衝動性)은 이 장애의 중심증상이 아니거나, 이들 약물투여에 의해 호전되지 않거나, 호전의 측정에 문제가 있을 수도 있겠다. 마지막으로 주의력결핍(注意力缺乏)${\cdot}$과잉운동장애(過剩運動障碍)에서 과잉행동(過剩行動)과 주의력결핍(注意力缺乏)이 서로 다른 신경전달체계(神經傳達體系)를 통해서 나타날 가능성에 대해서도 논의하였다.