对于 PC3 细胞，普罗替林（0-70 μM；24 小时）具有细胞毒性 [2]。

普罗替林（10 mg/kg；腹腔注射；21 天；AD 大鼠模型）可增强 STZ 治疗大鼠的空间学习能力并维持记忆力 [3]。

细胞毒性测定[2]
细胞类型： PC3 细胞
测试浓度： 50、60 和 70 μM
孵育时间：24小时
实验结果：细胞活力以浓度依赖性方式减弱。

Animal/Disease Models: AD rat model [3]
Doses: 10 mg/kg
Route of Administration: intraperitoneal (ip) injection; 21 days.
Experimental Results: diminished pTau, Aβ42 and BACE-1 levels, neurodegeneration, oxidative stress and glial activation. By reducing NFκB and GFAP expression, improving p-ERK/ERK ratio and increasing BDNF and CREB levels.

Absorption, Distribution and Excretion
Protriptyline is reported to undergo cumulative urinary excretion during 16 days, which accounts for approximately 50% of the total drug administered. The fecal excretion pathway seems to play a minimal role in drug elimination.
EXCRETION...IS RAPID, IN CONTRAST TO LONG LATENCY OF ONSET OF ACTION OF DRUGS. /TRICYCLIC ANTIDEPRESSANTS/
...WELL ABSORBED FROM GI TRACT. ... RAPIDLY DISTRIBUTED & METABOLIZED BY DEMETHYLATION, OXIDATION, & AROMATIC HYDROXYLATION. /IMIPRAMINE/
IN URINE OF RATS TREATED WITH PROTRIPTYLINE... THERE WAS TWICE AS MUCH 10,11-DIHYDRO-10,11-EPOXY-5-(3-METHYLAMINOPROPYL)-5H-DIBENZO[A,D]CYCLOHEPTENE AS 10,11-DIHYDRO-10,11-EPOXY-5-(3-AMINOPROPYL)-5H-DIBENZO[A,D]CYCLOHEPTENE EXCRETED &.../BOTH/ ACCOUNTED FOR 40% OF DOSE OF PROTRIPTYLINE.
MEAN PLASMA LEVELS FOR PROTRIPTYLINE IN PT ALSO ADMIN NITRAZEPAM INDISTINGUISHABLE FROM PT RECEIVING NO NITRAZEPAM. MEAN PLASMA LEVELS FOR PT RECEIVING SODIUM AMYLOBARBITONE SIGNIFICANTLY DECR. EARLY VALUES MAY BE OF PREDICTIVE IMPORTANCE TO PERMIT EARLY DOSE ADJUSTMENT.

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Metabolism / Metabolites
KNOWN OXIDATION OF 10,11 DOUBLE BOND OF PROTRIPTYLINE IN MAN, MINIATURE PIG, & DOG... 2 METABOLITES HAVE BEEN DETECTED WHICH DEMONSTRATE EPOXIDE INTERMEDIATE, NAMELY, DIHYDRODIOL & REARRANGEMENT PRODUCT WHOSE FORMATION IS...CATIONIC INTERMEDIATE...REARRANGING TO DIHYDROANTHRACENIC STRUCTURE.
IN DOGS, MINIATURE PIGS, & MAN, 3 URINARY METABOLITES HAVE NOW BEEN FOUND 10-HYDROXY-N-METHYL-5H-DIBENZO(AD)CYCLOHEPTENE-5-PROPYLAMINE, 10,11-DIHYDROXY-N-METHYL-5H-DIBENZO(AD)CYCLOHEPTENE-5-PROPYLAMINE & 5,10-DIHYDRO-10-FORMYLANTHRACENE-5-PROPYLAMINE.
...PROTRIPTYLINE...AFFORDS URINARY 10,11-OXIDE.
IN URINE OF RATS TREATED WITH PROTRIPTYLINE...2 METABOLITES HAVE BEEN IDENTIFIED...AS 10,11-DIHYDRO-10,11-EPOXY-5-(3-M ETHYLAMINOPROPYL)-5H-DIBENZO[A,D]CYCLOHEPTENE & 10,11-DIHYDRO-10,11-EPOXY-5-(3-AMINOPROPYL)-5H-DIBENZO[A,D]CYCLOHEPTENE.
Route of Elimination: Cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. The fecal route of excretion did not seem to be important.

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Biological Half-Life
AFTER A SINGLE ORAL DOSE OF 30 MG TO 8 SUBJECTS, PEAK LEVELS RANGED FROM 10.4-22.3 NG/ML, 6-12 HR AFTER ADMIN. MEAN T/2 WAS 74.3 HR & RANGED FROM 53.6-91.7 HR IN INDIVIDUAL SUBJECTS.
SINGLE ORAL DOSE OF HCL-SALT ADMIN TO 8 PERSONS. EST 1ST PASS METAB WAS RELATIVELY SMALL, 10-25% OF DOSE, ASSUMING COMPLETE ABSORPTION. MEAN VOL OF DISTRIBUTION 22.5 L/KG & RANGED FROM 15.0-31.2 L/KG. CONCLUSION WAS THAT LONG T/2 IS CORRELATED WITH SMALL 1ST PASS METABOLISM.
PLASMA LEVELS IN 30 PT. AFTER 3.5 WK TREATMENT @ 40 MG/DAY, PLASMA LEVELS RANGED FROM 430-1430 NMOL/L. SINGLE DOSE STUDIES IN 5 VOLUNTEERS SUGGEST THAT VOL OF DISTRIBUTION OF PROTRIPTYLINE SHOWS LITTLE INTERSUBJECT VARIATION. HOWEVER, T/2 MAY VARY, RANGING FROM 54-198 HR.

Toxicity Summary
Protriptyline acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).

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Interactions
Other interactions that also may potentiate the effects of tricyclic antidepressants can result from interference with their metabolism in the liver. This effect has been associated with neuroleptic drugs, methylphenidate, and certain steroids, including oral contraceptives. /Tricyclic antidepressants/
TRICYCLIC ANTIDEPRESSANTS MAY ENHANCE EFFECTS OF ORAL ANTICOAGULANTS. /TRICYCLIC ANTIDEPRESSANTS/
A PARTICULARLY SEVERE, BUT RARE, DRUG-DRUG INTERACTION HAS BEEN NOTED FOLLOWING THE CONCURRENT ADMINISTRATION OF AN MAO INHIBITOR AND A TRICYCLIC ANTIDEPRESSANT. /TRICYCLIC ANTIDEPRESSANTS/
THIS AGENT IS ALSO CONTRAINDICATED IN PT TAKING ANY OF MAO INHIBITOR ANTIDEPRESSANTS, SUCH AS NIALAMIDE, ISOCARBOXAZID, TRANYLCYPROMINE, OR PHENELZINE. /HYDROCHLORIDE/
For more Interactions (Complete) data for PROTRIPTYLINE (32 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 240 mg/kg
LD50 Rat ip 42 mg/kg
LD50 Mouse oral 269 mg/kg
LD50 Mouse ip 67 mg/kg
For more Non-Human Toxicity Values (Complete) data for PROTRIPTYLINE (8 total), please visit the HSDB record page.

[1]. Bansode SB, et, al. Molecular investigations of protriptyline as a multi-target directed ligand in Alzheimer's disease. PLoS One. 2014 Aug 20;9(8):e105196.
[2]. Chang HT, et, al. The mechanism of protriptyline-induced Ca2+ movement and non-Ca2+-triggered cell death in PC3 human prostate cancer cells. J Recept Signal Transduct Res. 2015;35(5):429-34.
[3]. Tiwari V, et, al. Protriptyline improves spatial memory and reduces oxidative damage by regulating NFκB-BDNF/CREB signaling axis in streptozotocin-induced rat model of Alzheimer's disease. Brain Res. 2021 Mar 1;1754:147261.

Protriptyline is a carbotricyclic compound. It has a role as an antidepressant. It derives from a hydride of a dibenzo[a,d][7]annulene.
Protriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, protriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, protriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H1 receptors, alpha1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Protriptyline may be used for the treatment of depression.
Protriptyline is a Tricyclic Antidepressant.
Protriptyline is a tricyclic antidepressant that was previously widely used in the therapy of major depression. Most of the tricyclic antidepressants have been shown to cause a low rate of mild and transient serum enzyme elevations and rare cases of clinically apparent acute cholestatic liver injury. The potential hepatotoxicity specifically of protriptyline, however, has not been well defined.
Protriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, protriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, protriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H₁ receptors, α₁-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Protriptyline may be used for the treatment of depression.
Tricyclic antidepressant similar in action and side effects to IMIPRAMINE. It may produce excitation.
See also: Protriptyline Hydrochloride (has salt form).

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Drug Indication
For the treatment of depression.

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Mechanism of Action
Protriptyline acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).
ACTION OF TRICYCLIC ANTIDEPRESSANTS ON METAB OF CATECHOLAMINES & INDOLEAMINES IN BRAIN HAS CONTRIBUTED SIGNIFICANTLY TO "BIOGENIC AMINE HYPOTHESIS" OF DEPRESSION. ... /ALL/ BLOCK RE-UPTAKE OF NOREPINEPHRINE BY ADRENERGIC NERVE TERMINALS. /DEMETHYLATED ANALOGS ARE MORE POTENT IN THIS ACTION/ /TRICYCLIC ANTIDEPRESSANTS/

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Therapeutic Uses
Adrenergic Uptake Inhibitors; Antidepressive Agents, Tricyclic
TRICYCLIC (DIBENZOCYCLOHEPTENE) ANTIDEPRESSANT DRUG USEFUL IN MGMNT OF ENDOGENOUS & EXOGENOUS DEPRESSIONS. IT ALSO INCR PSYCHOMOTOR ACTIVITY; THIS PROPERTY ENHANCES ITS USE IN WITHDRAWN & ANERGIC PT. /HYDROCHLORIDE/
...MAY BE PARTICULARLY USEFUL IN TREATING DEPRESSED PT WHOSE PREDOMINANT MANIFESTATIONS OF ILLNESS ARE PSYCHOMOTOR RETARDATION, APATHY, & FATIGUE... /HYDROCHLORIDE/
...BECAUSE OF THEIR SEDATIVE PROPERTY. ...MAY BE USEFUL IN INITIAL THERAPY OF DEPRESSED PT WITH SLEEP LOSS... DRUGS DO DECR NUMBER OF AWAKENINGS, INCR STAGE-4 SLEEP, & MARKEDLY DECR REM TIME. /TRICYCLIC ANTIDEPRESSANTS/
For more Therapeutic Uses (Complete) data for PROTRIPTYLINE (8 total), please visit the HSDB record page.

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Drug Warnings
...POSSESSES ANTICHOLINERGIC PROPERTIES &, HENCE, SHOULD NOT BE USED IN PT WITH PYLORIC OBSTRUCTION, GLAUCOMA, OR URINARY RETENTION. /HYDROCHLORIDE/
...THOSE WITH SYMPTOMS OF AGITATION, ANXIETY, & TENSION FREQUENTLY BECOME MORE DISTURBED WITH USE OF PROTRIPTYLINE.
DRUG MAY AGGRAVATE ANXIETY, & IT SHOULD NOT BE USED IN ANXIOUS DEPRESSED PT UNLESS IT IS GIVEN WITH SEDATIVE DRUG, SUCH AS PHENOTHIAZINE WITH SEDATIVE EFFECTS...OR MORE CONVENTIONAL SEDATIVE DRUG... /HYDROCHLORIDE/
TACHYCARDIA & POSTURAL HYPOTENSION OCCUR MORE FREQUENTLY...THAN WITH OTHER ANTIDEPRESSANT DRUGS; HENCE, PT WITH CARDIOVASCULAR DISORDERS & ELDERLY PT SHOULD BE OBSERVED CLOSELY FOR THESE UNTOWARD EFFECTS. /HYDROCHLORIDE/
For more Drug Warnings (Complete) data for PROTRIPTYLINE (28 total), please visit the HSDB record page.

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Pharmacodynamics
Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin by nerve cells. The effectiveness of antidepressants appear after approximately two weeks following recommended adminsitration schedule. Gradual changes are thought to occur in the cerebral cortex and hippocampus, involved in emotion regulation as part of the limbic system, as receptor sensitivity is enhanced. While α₁ and β₁ receptors are sensitized, α₂ receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also reported to alter the perceptions of pain, including neuropathic or neuralgic pain, so they may exhibit analgesic properties. The mechanism of action behind this analgesic property is not fully understood; however, it is thought to involve modulation of endogenous opioid systems in the CNS via an indirect serotonergic route. Tricyclic antidepressants are also effective in relieving migraine prophylaxis, but not in abortion of acute migraine attack, potentially via their serotonergic effects.

C19H21N

263.167

438-60-8

Protriptyline hydrochloride;1225-55-4;Protriptyline-d3;136765-50-9

4976

Typically exists as solid at room temperature

1.026 g/cm3

407.7ºC at 760 mmHg

169-171 °C (Protriptyline HCl)
Max absorption 290 nm (e= 13,311); MP: 169-171 °C; crystals from isopropanol- ethyl ether /hydrochloride/
169 - 171 °C (protriptyline hydrochloride)

198.3ºC

4.692

12.03

1

1

4

20

296

0

CNCCCC1C2=CC=CC=C2C=CC3=CC=CC=C31

BWPIARFWQZKAIA-UHFFFAOYSA-N

InChI=1S/C19H21N/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19/h2-5,7-10,12-13,19-20H,6,11,14H2,1H3

N-methyl-3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenyl)propan-1-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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;
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