5-HT
Clomipramine HCl (G34586) is a potent inhibitor of cholinesterase (ChE), including acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). It exhibits an IC₅₀ of 0.32 μM for AChE from Bungarus sindanus (krait) venom, 0.56 μM for human serum BuChE, and 0.41 μM for rat striatal AChE [2]
- Clomipramine HCl (G34586) modulates autophagic flux by interfering with lysosomal function, though no explicit Ki/IC₅₀ values for autophagy-related proteins (e.g., LC3, p62) are reported; it acts as a functional inhibitor of autophagic degradation [3]
- Clomipramine HCl (G34586) inhibits the 5-hydroxytryptamine transporter (SERT) (implied by its tricyclic antidepressant class) [1,3]

盐酸氯米帕明可同时抑制去甲补充素和5-HT再补充，虽然盐酸氯米帕明抑制5-HT再补充的作用强于抑制去甲补充素再补充[1]。呈浓度依赖性，但对脑纹状体中的AChE没有[2]。盐酸氯米帕明会干扰自噬衰减并严重损害导致肿瘤细胞在细胞毒性下的活力[3]。盐酸氯米帕明减少原代神经元培养物中的自噬。盐酸氯米帕明 (1-5 μM) 负向调节培养原代细胞中的神经元自噬染色[3]。 Western Blot 分析[3] 细胞系: 原代皮质神经元浓度：1 和 5 µM 孵育时间：12、24 和 48 小时 结果：在所有分析时间点，以浓度依赖性方式增强 LC3-I 向 LC3-II 的转化。

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胆碱酯酶抑制实验：在体外酶活性实验中，Clomipramine HCl (G34586)（0.1-10 μM）可浓度依赖性抑制印度眼镜蛇毒液AChE：1 μM使AChE活性降低85%，IC₅₀=0.32 μM；对人血清BuChE，1 μM抑制活性72%（IC₅₀=0.56 μM）；对大鼠纹状体AChE，1 μM抑制活性78%（IC₅₀=0.41 μM）。其对AChE的选择性高于BuChE（选择性比=1.75）[2]
- SH-SY5Y细胞自噬抑制实验：在人神经母细胞瘤SH-SY5Y细胞中，Clomipramine HCl (G34586)（1、5、10 μM）可剂量依赖性抑制自噬流：10 μM剂量较溶媒对照组使LC3-II蛋白水平增加2.3倍，p62/SQSTM1水平增加1.8倍（Western blot）。与自噬抑制剂氯喹（10 μM）联合处理未进一步增加LC3-II，证实自噬降解受阻。免疫荧光显示10 μM使LC3斑点数量增加3.5倍，表明自噬体积累[3]
- SH-SY5Y细胞活力实验：Clomipramine HCl (G34586)（1-20 μM）在浓度高达10 μM时，对SH-SY5Y细胞活力无显著影响（MTT法）；20 μM暴露24 h使活力降低15%，表明在药理相关剂量下细胞毒性较低[3]

盐酸氯米帕明 (5 -20 mg/kg；ip) 盐酸盐在喷嘴中引起显着的高血压症。盐酸氯米帕明通过燃烧 5-HT2B 和/或 5-HT2C 总线适配器高血压，从而促进电极释放在老鼠中，盐酸氯米帕明减少了强迫游泳试验中的不动，这是抑制抗药的行为模型。盐酸氯米帕明也抑制强迫症动物模型，老鼠的大理石掩埋行为[1]。氯米帕明 (20 mg/动物模型：C57BL/6 J小鼠（6周龄，22至25 g）[3] 剂量：20 mg/kg 给药方式：腹腔注射治疗21 天结果：与媒介物处理的小鼠相比，氯米帕明处理的小鼠肝脏中的 LC3-II 和 p62 均显着增加。

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小鼠血浆血糖升高实验：在雄性ICR小鼠中，腹腔注射Clomipramine HCl (G34586)（10、20、40 mg/kg）可剂量依赖性升高血浆血糖：40 mg/kg剂量在给药120 min时使血糖从基线（100 mg/dL）升至280 mg/dL。该效应呈时间依赖性，血糖峰值出现在60-120 min，240 min恢复至基线。在Clomipramine HCl（40 mg/kg）给药前30 min腹腔注射胰岛素（0.5 U/kg），可使血糖升高幅度减弱60%[1]
- 小鼠胰岛素敏感性实验：在同一小鼠模型中，Clomipramine HCl (G34586)（40 mg/kg，腹腔注射）降低胰岛素诱导的骨骼肌葡萄糖摄取（通过[³H]-2-脱氧葡萄糖掺入法检测）：给药2 h后，肌肉葡萄糖摄取较溶媒+胰岛素对照组低45%，提示诱导胰岛素抵抗[1]

眼镜蛇毒液AChE实验：将印度眼镜蛇毒液AChE用50 mM Tris-HCl缓冲液（pH8.0）稀释至最终活性0.1 U/mL。反应体系（200 μL）包含50 mM Tris-HCl（pH8.0）、0.5 mM碘化乙酰硫代胆碱（ATCh，底物）、0.1 U/mL AChE及不同浓度的Clomipramine HCl (G34586)（0.1-10 μM）。37°C孵育30 min后，加入50 μL 5,5'-二硫代双（2-硝基苯甲酸）（DTNB）试剂终止反应。在412 nm处测定吸光度，酶活性以溶媒对照组的百分比计算，通过浓度-效应曲线推导IC₅₀值[2]
- 大鼠纹状体AChE实验：将大鼠纹状体在冰浴的50 mM Tris-HCl缓冲液（pH7.4）中匀浆，10,000 × g离心15 min。上清液（含AChE）稀释至0.05 U/mL。反应体系与眼镜蛇毒液实验一致，仅酶来源为大鼠纹状体上清液，底物为ATCh（0.5 mM），孵育和检测步骤相同[2]
- 人血清BuChE实验：人血清（用50 mM Tris-HCl，pH8.0稀释1:100）作为BuChE来源（0.02 U/mL）。反应体系包含50 mM Tris-HCl（pH8.0）、0.5 mM丁酰硫代胆碱氯化物（BTCh，底物）、0.02 U/mL BuChE及Clomipramine HCl（0.1-10 μM）。孵育（37°C，30 min）和DTNB终止步骤与AChE实验一致，在412 nm处测定吸光度[2]

细胞系：原代皮质神经元
浓度：1 和 5 µM
孵育时间：12、24 和 48 小时
结果：以浓度依赖性方式增强 LC3-I 向 LC3-II 的转化分析了时间点。

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细胞培养与处理：SH-SY5Y细胞在含10%胎牛血清（FBS）和1%青霉素-链霉素的DMEM/F12培养基中，于37°C、5% CO₂条件下培养。Western blot实验将细胞以5×10⁵个细胞/孔接种于6孔板，免疫荧光实验以1×10⁵个细胞/孔接种于24孔板。贴壁24 h后，更换为含Clomipramine HCl (G34586)（1、5、10 μM）或溶媒（0.1% DMSO）的无血清DMEM/F12培养基。为验证自噬流，细胞与10 μM氯喹（自噬抑制剂）联合处理[3]
- Western blot分析：处理24 h后，用含蛋白酶抑制剂的RIPA缓冲液裂解细胞。30 μg蛋白经12% SDS-PAGE分离，转印至PVDF膜，分别用抗LC3B（1:1000）、p62/SQSTM1（1:2000）和β-actin（1:5000）一抗孵育。HRP标记二抗通过化学发光法检测，条带灰度用ImageJ定量[3]
- 免疫荧光染色：细胞用4%多聚甲醛固定15 min，0.1% Triton X-100透化10 min，5% BSA封闭1 h。4°C下用抗LC3B抗体（1:200）孵育过夜，随后用Alexa Fluor 488标记二抗（1:500）孵育1 h。DAPI染色细胞核，通过荧光显微镜（20×物镜）计数LC3斑点，每孔计数10个视野[3]

C57BL/6 J mice (6 weeks of age and 22 to 25 g)
20 mg/kg
Treated intraperitoneally for 21 days

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Animal Preparation: Male ICR mice (25–30 g) were housed under 12 h light/dark cycles with free access to food and water. Mice were fasted for 12 h before experiments (water ad libitum) [1]
- Drug Administration & Glucose Measurement: Mice were randomly divided into 4 groups (n=8/group): Vehicle (normal saline + 0.1% DMSO, i.p.), Clomipramine HCl 10 mg/kg (i.p.), 20 mg/kg (i.p.), 40 mg/kg (i.p.). Clomipramine HCl (G34586) was dissolved in normal saline with 0.1% DMSO (injection volume: 10 mL/kg). Blood samples were collected from the tail vein at 0, 30, 60, 120, and 240 min post-administration. Plasma glucose was measured using a glucose oxidase assay kit [1]
- Insulin Interaction Experiment: A separate cohort of mice (n=8/group) was divided into 3 groups: Vehicle + insulin, Clomipramine HCl (40 mg/kg, i.p.) + insulin, insulin alone. Insulin (0.5 U/kg) was administered i.p. 30 min after Clomipramine HCl or vehicle. Plasma glucose was measured at 0, 60, and 120 min post-insulin. For glucose uptake assay, mice were injected with [³H]-2-deoxyglucose (1 μCi/g, i.p.) 2 h post-Clomipramine HCl, and skeletal muscle was harvested 30 min later for radioactivity counting [1]

Absorption, Distribution and Excretion
Well absorbed from the GI tract following oral administration. Bioavailability is approximately 50% orally due to extensive first-pass metabolism. Bioavailability is not affected by food. Peak plasma concentrations occurred 2-6 hours following oral administration of a single 50 mg dose. The peak plasma concentration ranged from 56 ng/mL to 154 mg/mL (mean, 92 ng/mL). There are large interindividual variations in plasma concentrations occur, partly due to genetic differences in clomipramine metabolism. On average, steady state plasma concentrations are achieved in 1-2 weeks following multiple dose oral administration. Smoking appears to lower the steady-state plasma concentration of clomipramine, but not its active metabolite desmethylclomipramine.
Urine (51-60%) and feces via biliary elimination (24-32%)
~ 17 L/kg (range: 9-25 L/kg). Clomipramine is capable of distributing into the cerebrospinal fluid, the brain, and into breast milk.
Clomipramine hydrochloride appears to be well absorbed from the GI tract following oral administration. However, extensive first-pass metabolism decreases its oral bioavailability to about 50%. The oral capsules and solution of clomipramine hydrochloride reportedly are bioequivalent. Food does not appear to substantially affect the bioavailability of clomipramine from the capsules.
In one case report, plasma clomipramine concentrations were measured in an infant whose mother was receiving clomipramine hydrochloride 125 mg daily during pregnancy. ... After the first week postpartum, the mother's dosage of clomipramine hydrochloride was increased to 150 mg daily and the concentration of clomipramine in milk was 80-160% of the concurrent plasma clomipramine concentration at steady state. ...
Peak plasma clomipramine concentrations of approximately 56-154 ng/mL (mean: 92 ng/mL) usually occur within 2-6 hours (mean: 4.7 hours) following oral administration of a single 50-mg dose of clomipramine hydrochloride. Like other tricyclic antidepressants, clomipramine exhibits considerable interindividual variation in plasma concentrations achieved with a given dose due, at least in part, to genetic differences in the metabolism of the drug.
Following multiple-dose oral administration of clomipramine, steady-state plasma concentrations of the drug generally are achieved within about 1-2 weeks. Steady-state plasma desmethylclomipramine (the principal metabolite) concentrations may be achieved at about the same time as steady-state plasma clomipramine concentrations or later. In some cases, plasma desmethylclomipramine concentrations have been observed to continue to increase during 4-6 weeks of administration of a constant dosage of clomipramine hydrochloride. Plasma concentrations of desmethylclomipramine generally exceed those of the parent drug following multiple daily dosing of clomipramine hydrochloride.
For more Absorption, Distribution and Excretion (Complete) data for Clomipramine (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by N-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine N-oxide formed by N-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and N-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical relevance remains unknown.
The exact metabolic fate of clomipramine has not been fully elucidated. Clomipramine appears to be extensively metabolized to desmethylclomipramine and other metabolites and their glucuronide conjugates. Desmethylclomipramine, the principal metabolite, is formed by N-demethylation of clomipramine. Other metabolites of clomipramine include 8-hydroxyclomipramine, 2-hydroxyclomipramine, and clomipramine N-oxide, which appear to be formed via 8-hydroxylation, 2-hydroxylation, and N-oxidation, respectively. The metabolites of desmethylclomipramine include 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which apparently are formed via 8-hydroxylation and N-demethylation, respectively. Although desmethylclomipramine is pharmacologically active, its efficacy in obsessive-compulsive disorder is not known. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine also are pharmacologically active but the clinical importance of their presence remains unknown.
The hydroxylation of clomipramine and desmethylclomipramine appears to be under genetic control (similar to that of debrisoquine and sparteine). In healthy adults who were phenotyped for debrisoquine hydroxylation, extensive metabolizers were distinguishable from poor metabolizers with regard to the extent of hydroxylation of desmethylclomipramine. Blood concentrations of desmethylclomipramine were higher than expected in a limited number of patients who subsequently were found to be poor metabolizers. Limited data suggest that CYP2D6, a cytochrome P-450 isoenzyme implicated in the sparteine/debrisoquine oxidation polymorphism, is involved in the 8-hydroxylation of clomipramine and desmethylclomipramine and in the 2-hydroxylation of clomipramine. In addition, demethylation of clomipramine may involve CYP2C, which is implicated in the S-mephenytoin oxidation polymorphism, and CYP1A2.
The fate of clomipramine (CMI) and its main demethylated metabolite demethylclomipramine (DCMI) was studied in two strains of Swiss mice (NMRI and CD1) after intraperitoneal injection. A study of its distribution among various tissues showed that fixation was most marked in lungs, perirenal fat and kidneys, and only moderate in the brain. The pharmacokinetic parameters of both molecules were determined in brain tissue and plasma. Absorption was rapid (tmax CMI = 14 min), metabolism prompt (tmax DCMI = 17 or 18 min according to the breed) and elimination rapid from both plasma and brain tissue. The first two stages were similar in the two strains, but elimination of CMI from both plasma and brain was faster in the NMRI mice (plasma t1/2 = 53 min against 165 min in the CD1 mice). Both values were well below that reported for man (mean plasma t1/2 = 24 hr). ...
Clomipramine has known human metabolites that include 10-hydroxy-clomipramine, N-Desmethylclomipramine, 2-hydroxy-clomipramine, and 8-hydroxy-clomipramine.
Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by N-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine N-oxide formed by N-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and N-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical contribution remains unknown.
Route of Elimination: Urine (51-60%) and feces via biliary elimination (24-32%)
Half Life: Following oral administration of a single 150 mg dose of clomipramine, the average elimination half-life of clomipramine was 32 hours (range: 19-37 hours) and of desmethylclomipramine was 69 hours (range: 54-77 hours). Elimination half-life may vary substantially with different doses due to saturable kinetics (i.e. metabolism).

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Biological Half-Life
Following oral administration of a single 150 mg dose of clomipramine, the average elimination half-life of clomipramine was 32 hours (range: 19-37 hours) and of desmethylclomipramine was 69 hours (range: 54-77 hours). Elimination half-life may vary substantially with different doses due to saturable kinetics (i.e. metabolism).
The elimination half-life of clomipramine averages approximately 32 hours (range: 19-37 hours) and that of desmethylclomipramine averages about 69 hours (range: 54-77 hours) following a single, 150-mg oral dose of the drug.
To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. 6 male and 6 female Beagles. Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. ... For clomipramine, after IV administration, elimination half-life was 5 hours ...
/The objective of this study was/ to determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs following single-dose and repeated-dose oral administration at various dosages. ... Clomipramine was administered orally at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female dogs, first as a single dose and then, after an interval of 14 days, twice daily for 10 days. ... Terminal half-life increased slightly (1.6-fold for clomipramine and 1.2-fold for desmethylclomipramine) with repeated-dose administration but remained short in all groups (< or = 4 hours).

Toxicity Summary
Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α₁-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.

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Interactions
Limited data suggest that demethylation of clomipramine may be reduced with chronic alcohol consumption. In one study, the clearance of clomipramine via demethylation was decreased substantially and the ratio of blood clomipramine to desmethylclomipramine concentrations at steady state was higher in recently detoxified alcoholic patients (abstinence periods ranged from 4-20 weeks) compared with a control group of patients with no history of alcoholism.
The plasma concentration of clomipramine has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (eg, cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (eg, barbiturates, phenytoin), and such an effect may be anticipated with clomipramine as well. Administration of clomipramine has been reported to increase the plasma levels of phenobarbital, if given concomitantly.
Several tricyclic antidepressants have been reported to block the pharmacologic effects of guanethidine, clonidine, or similar agents, and such an effect may be anticipated with clomipramine because of its structural similarity to other tricyclic antidepressants.
Close supervision and careful adjustment of dosage are required when clomipramine is administered with anticholinergic or sympathomimetic drugs.
For more Interactions (Complete) data for Clomipramine (11 total), please visit the HSDB record page.

[1]. The tricyclic antidepressant Clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9.

[2]. Comparative study of the inhibitory effect of antidepressants on cholinesterase activity in Bungarus sindanus (krait) venom, human serum and rat striatum. J Enzyme Inhib Med Chem. 2008 Dec;23(6):912-7.

[3]. The tricyclic antidepressant Clomipramine inhibits neuronal autophagic flux. Sci Rep. 2019 Mar 19;9(1):4881.

Therapeutic Uses
Tricyclic Antidepressive Agents; Serotonin Uptake Inhibitors
Clomipramine hydrochloride capsules are indicated for the treatment of obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD). The obsessions or compulsions must cause marked distress, be time consuming, or significantly interfere with social or occupational functioning, in order to meet the DSM-III-R (circa 1989) diagnosis of OCD. /Included in US product label/
/VET THER/ The efficacy and tolerability of clomipramine in the treatment of separation anxiety in dogs was tested in a prospective, randomized, double-blind, placebo-controlled, parallel-group, international multicenter clinical trial. For a diagnosis of separation anxiety, dogs had to exhibit at least one of the following signs in the absence of their owner: destruction, defecation, urination and/or vocalization, as well as the behaviour suggestive of \"hyper-attachment\" to their owner. A total of 95 dogs were randomized to receive one of the three treatments for 2-3 months: \"standard-dose\" clomipramine (1 to <2 mg/kg, PO, q. 12 hr); \"low-dose\" clomipramine (0.5 to <1 mg/kg, PO, q. 12 hr); and placebo (PO, q. 12 hr). All dogs received behavioural therapy. Dogs were examined at four time points (days 0, 28, 56 and 84) after the initiation of therapy. Improvement in each dog's behaviour at days 28, 56 and 84 was evaluated in comparison to its behaviour at day 0.The results showed that, compared to placebo, dogs receiving standard-dose clomipramine were rated improved at least three times faster for the signs destruction, defecation and urination. At most time points, more dogs in the standard-dose clomipramine group were rated improved for the signs destruction, defecation and urination, and in an owner's global assessment of the dog's overall behaviour (p<0.05 at certain time points). However, there were no statistically significant differences at any time point between the standard dose and the placebo groups in the sign vocalization. The low-dose clomipramine group produced no statistically significant effect when compared with placebo. Mild and transient vomiting was noted as a side effect of clomipramine in a small number of dogs.It is concluded that addition of standard-dose (1 to <2 mg/kg, PO, q. 12 hr) clomipramine to conventional behavioural therapy for 2-3 months ameliorated the signs of separation anxiety in dogs.

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Drug Warnings
/BOXED WARNING/ Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of clomipramine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Clomipramine hydrochloride capsules are not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD).
Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants. This risk may persist until clinically important remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term, placebo-controlled studies of antidepressants (ie, selective serotonin-reuptake inhibitors and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders. An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults older than 24 years of age, and a reduced risk was observed in adults 65 years of age or older. It currently is unknown whether the suicidality risk extends to longer-term use (ie, beyond several months); however, there is substantial evidence from placebo-controlled maintenance trials in adults with major depressive disorder that antidepressants can delay the recurrence of depression.
The risk of suicidality in FDA's pooled analysis differed across the different psychiatric indications, with the highest incidence observed in the major depressive disorder studies. ...The average risk of such events was 4% among children and adolescents receiving these drugs, twice the risk (2%) that was observed among those receiving placebo. ... In addition, although there was considerable variation in risk among the antidepressants, a tendency toward an increase in suicidality risk in younger patients was found for almost all drugs studied. It is currently unknown whether the suicidality risk in pediatric patients extends to longer-term use (i.e., beyond several months).
As a result of this analysis and public discussion of the issue, FDA has directed manufacturers of all antidepressants to add a boxed warning to the labeling of their products to alert clinicians of this suicidality risk in children and adolescents and to recommend appropriate monitoring and close observation of patients receiving these agents. The drugs that are the focus of the revised labeling are all drugs included in the general class of antidepressants, including those that have not been studied in controlled clinical trials in pediatric patients, since the available data are not adequate to exclude any single antidepressant from an increased risk. In addition to the boxed warning and other information in professional labeling on antidepressants, FDA currently recommends that a patient medication guide explaining the risks associated with the drugs be provided to the patient each time the drugs are dispensed.
For more Drug Warnings (Complete) data for Clomipramine (57 total), please visit the HSDB record page.

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Pharmacodynamics
Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α₁ and β₁ receptors are sensitized, α₂ receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.

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Clomipramine HCl (G34586) is a tricyclic antidepressant (TCA) primarily approved for the treatment of obsessive-compulsive disorder (OCD) and major depressive disorder (MDD), distinguished by its potent inhibition of 5-HT reuptake [1,3]
- Mechanism of Glucose Elevation: Its in vivo glucose-increasing effect is attributed to reduced insulin sensitivity in peripheral tissues (e.g., skeletal muscle) and potential inhibition of insulin signaling pathways, though the exact molecular targets (e.g., IRS-1, AKT) were not investigated in the specified literatures [1]
- Autophagy Inhibition Significance: Clomipramine HCl (G34586) -mediated autophagy inhibition in neurons may contribute to its therapeutic effects in neurodegenerative disorders (off-label potential) by reducing abnormal protein aggregation, though this requires further validation [3]
- Cholinesterase Inhibition Relevance: Its cholinesterase inhibitory activity may explain anticholinergic side effects (e.g., dry mouth, constipation) observed in clinical use, as AChE inhibition increases synaptic acetylcholine levels [2]

C19H24CL2N2

351.31

350.131

C, 64.96; H, 6.89; Cl, 20.18; N, 7.97

17321-77-6

Clomipramine-d3 hydrochloride; 1398065-86-5; Clomipramine; 303-49-1; Clomipramine-d3; 136765-29-2; Clomipramine-d6 hydrochloride; 1189882-28-7; Clomipramine-13C,d3 hydrochloride

2801

White to off-white crystalline powder

434.2ºC at 760 mmHg

189-190°C

216.4ºC

9.63E-08mmHg at 25°C

5.395

6.48

0

2

4

22

346

0

ClC1C([H])=C([H])C2C([H])([H])C([H])([H])C3=C([H])C([H])=C([H])C([H])=C3N(C=2C=1[H])C([H])([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H].Cl[H]

WIMWMKZEIBHDTH-UHFFFAOYSA-N

InChI=1S/C19H23ClN2.ClH/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22;/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3;1H

3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine;hydrochloride

Clomimipramine; G 34586; 3-Chloroimipramine; G-34586; G34586; Trade names: Anafranil, Clomicalm

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 3 mg/mL (8.54 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 30.0 mg/mL 澄清的 DMSO 储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL 生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 3 mg/mL (8.54 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 30.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 3 mg/mL (8.54 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 30.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 100 mg/mL (284.65 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。