Human D₁ Receptor ( Ki = 18 nM ); Human D₂ Receptor ( Ki = 2.96 nM ); Human D₃ Receptor ( Ki = 4.56 nM ); Human D₅ Receptor ( Ki = 9 nM ); Human H₁ Receptor ( Ki = 3.75 nM )

体外活性：Chlorprothixene 对多巴胺和组胺受体（如 D1、D2、D3、D5 和 H1）具有很强的结合亲和力，Ki 值分别为 18nM、2.96 nM、4.56 nM、9 nM 和 3.75 nM，但活性很小。对 H3 的亲和力 (Ki >1000 nM)。 Chlorprothixene 还对来自稳定转染的 HEK-293 细胞的大鼠 5-HT6 和来自瞬时表达的 COS-7 细胞的大鼠 5-HT7 受体表现出高亲和力，Ki 值分别为 3 nM 和 5.6 nM。施用氯普噻烯可抑制 Vero 76 细胞中的 SARS-CoV 复制，Urbani 株的 IC50 为 16.7 μM，Frankfurt-1 为 13.0 μM，CHUK-W1 为 18.5 μM，Toronto-2 为 15.8 μM。也有与丙嗪类似的检测结果。

Chlorprothixene 阻断大脑中突触后中脑边缘多巴胺能 D1 和 D2 受体，抑制下丘脑和垂体激素的释放。高剂量的氯普噻辛抑制异丙烟肼对利血平诱导的肾上腺髓质和脑中儿茶酚胺释放的保护作用，以及利血平或异丙烟肼引起的大鼠脑中5HT、NE和DA的减少。 Chlorprothixene 的给药可恢复小鼠支气管上皮细胞中正常的神经酰胺浓度，减少囊性纤维化 (CF) 小鼠肺部的炎症，并通过抑制酸性鞘磷脂酶 (Asm) 而不是中性鞘磷脂酶 (Nsm) 来预防铜绿假单胞菌感染。

Absorption, Distribution and Excretion
Incomplete bioavailability.
.../IT/ IS PARTIALLY ABSORBED FROM THE GI TRACT. FOLLOWING IM ADMIN, THE DRUG EXERTS ITS EFFECTS WITHIN 10-30 MINUTES. IT IS METABOLIZED, PRESUMABLY IN THE LIVER...FREE CHLORPROTHIXENE & ITS SULFOXIDE METABOLITE ARE EXCRETED IN THE URINE & FECES.
TRICYCLIC AGENT, CHLORPROTHIXENE, IS...EXTENSIVELY DISTRIBUTED IN BODY & HAS OVERALL DISTRIBUTION VOL IN MAN APPROACHING 1000 L...
AFTER IV ADMIN PHARMACOKINETICS FOLLOWED 2 COMPARTMENT MODEL. ...TOTAL VOL OF DISTRIBUTION WAS VERY LARGE. AFTER ORAL ADMIN (15 MG) BIOAVAILABILITY WAS POOR, ALTHOUGH ABSORPTION OF CMPD FROM THE GUT APPEARED TO BE GOOD.
METABOLISM OCCURRED MORE RAPIDLY WITH INCR AGE FROM 3-24 WK IN RATS. LEVELS OF CHLORPROTHIXENE, N-DEMETHYLCHLORPROTHIXENE & TOTAL AMINES IN BRAIN, LIVER, KIDNEYS & LUNG OF 3-WK OLD RATS WERE ABOUT TWICE THOSE IN 6-WK OLD RATS. AMT IN ORGANS WERE HIGHER IN FEMALES THAN IN MALES.
After 1 hour intravenous chlorprothixene infusion, the maximum serum concentration of chlorprothixene was 430 ng/ml, which subsequently decreased with a terminal elimination half-life of 25.8 hours. The total serum clearance and the apparent volume of distribution at steady state were 867 ml/min and 1035 l, respectively. ... Chlorprothixene bioavailability relative to the oral soution was 56.45 with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameterws showed wide inter-subject varioations.

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Metabolism / Metabolites
Hepatic
UNCHANGED CHLORPROTHIXENE, THE SULFOXIDE DERIVATIVE & N-DEMETHYL SULFOXIDE HAVE BEEN IDENTIFIED IN THE URINE OF TREATED DOGS & RATS. HYDROXYLATION & GLUCURONIDATION ALSO OCCUR IN DOGS, BUT IDENTIFICATION OF THOSE BIOTRANSFORMATION PRODUCTS HAS NOT BEEN ACCOMPLISHED.
YIELDS DEMETHYLCHLORPROTHIXENE IN RAT. /FROM TABLE/
FOLLOWING ORAL ADMIN TO DOG & PSYCHIATRIC PT SEVERAL 3-, 7-, 4-, 6-, & 8-HYDROXYLATED METABOLITES FOUND IN URINE & FECES. HYDROXYLATION WAS FOLLOWED BY CONJUGATION WITH GLUCURONIC &/OR SULFURIC ACID FOR EXCRETION.
DRUG ADMIN TO RATS BY GAVAGE AT 100 MG/KG WAS METABOLIZED MORE RAPIDLY WITH INCR AGE FROM 3-24 WK.

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Biological Half-Life
8 to 12 hours
AFTER IV ADMIN PHARMACOKINETICS FOLLOWED 2 COMPARTMENT MODEL. T/2 IN SECOND PHASE OF ELIMINATION WAS 5-12 HR...
TRICYCLIC AGENT, CHLORPROTHIXENE, ...HAS...BIOLOGICAL T/2 OF 8-12 HR.

Interactions
Concurrent use with alcohol or CNS depression-producing medications, anesthetics, barbiturates, and opioid (narcotic) analgesics may potentiate and prolong the CNS depressant effects of either these medications or the thioxanthenes; dosage adjustments may be necessary. /Thioxanthenes/
Concurrent use with thioxanthenes may inhibit the CNS-stimulating effects of amphetamines due to alpha-adrenergic blockage by the thioxanthenes; also, the antipsychotic effects of thioxanthenes may be reduced when they are used concurrently with amphetamines. /Thioxanthenes/
Concurrent use of antacids or adsorbent antidiarrheals may inhibit the absorption of an orally administered thioxanthene. /Thioxanthenes/
Anticholinergic effects, especially confusion, hallucinations, nightmares, and increased intraocular pressure, may be potentiated when anticholinergics or other medications with anticholinergic action, antidyskinetic agents, or antihistamines are used concurrently with thioxanthenes, because of secondary anticholinergic action of thioxanthenes. /Thioxanthenes/
For more Interactions (Complete) data for CHLORPROTHIXENE (18 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 380 mg/kg

[1]. Bioorg Med Chem Lett . 2009 Jan 15;19(2):538-42.

[2]. J Pharmacol Exp Ther . 1994 Mar;268(3):1403-10.

[3]. Antiviral Res . 2008 Aug;79(2):105-13.

[4]. J Pharmacol Exp Ther . 1961 Jul:133:18-24.

[5]. Am J Respir Cell Mol Biol . 2010 Jun;42(6):716-24.

(Z)-chlorprothixene is a chlorprothixene in which the double bond adopts a (Z)-configuration. It is an enantiomer of an (E)-chlorprothixene.
Chlorprothixene is a typical antipsychotic drug of the thioxanthene (tricyclic) class. Chlorprothixene exerts strong blocking effects by blocking the 5-HT2 D1, D2, D3, histamine H1, muscarinic and alpha1 adrenergic receptors.
A thioxanthine with effects similar to the phenothiazine antipsychotics.

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Drug Indication
For treatment of psychotic disorders (e.g. schizophrenia) and of acute mania occuring as part of bipolar disorders.

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Mechanism of Action
Chlorprothixene blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.
...IT CAN BE EXPECTED TO DEPRESS THE CNS AT THE SUBCORTICAL LEVEL OF THE BRAIN, THE MIDBRAIN, & THE BRAIN STEM RETICULAR FORMATION.
.../IT/ IS MORE ACTIVE THAN CHLORPROMAZINE IN INHIBITING POSTURAL REFLEXES & MOTOR COORDINATION & LESS ACTIVE IN ANTIHISTAMINIC EFFECTS. CHLORPROTHIXENE POSSESSES SEDATIVE, ADRENOLYTIC, HYPOTHERMIC, ANTICHOLINERGIC, & ANTIEMETIC PROPERTIES.
Thioxanthenes are thought to benefit psychotic conditions by blocking postsynaptic dopamine receptors in the brain. They also produce an alpha-adrenergic blocking effect and depress the release of most hypothalamic and hypophyseal hormones. However, the concentration of prolactin is increased due to blockade of prolactin inhibitory factor (PIF), which inhibits the release of prolactin from the pituitary gland. /Thioxanthenes/
Chlorprothixene also inhibits the medullary chemoreceptor trigger zone to produce an antiemetic effect, and is also thought to cause an indirect reduction of stimuli to the brain stem reticular system to produce a sedative effect.

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Therapeutic Uses
Antipsychotic Agents; Dopamine Antagonists
IT MAY BE OF VALUE IN THE SYMPTOMATIC TREATMENT OF AGITATED STATES ASSOCIATED WITH NEUROSES, DEPRESSION OR SCHIZOPHRENIA. DRUG APPEARS TO BE MORE EFFECTIVE IN THE MANAGEMENT OF ACUTE SCHIZOPHRENIA THAN OF CHRONIC SCHIZOPHRENIA.
...IT HAS BEEN USED IN THE TREATMENT OF...PSYCHOTIC & SEVERE NEUROTIC CONDITIONS IN WHICH ANXIETY, AGITATION, AND TENSION PREDOMINATE.
.../IT/ MAY BE USED TO POTENTIATE CENTRAL NERVOUS SYSTEM DEPRESSANTS & CONCOMITANTLY WITH ANTICONVULSANTS &/OR ELECTROSHOCK TREATMENT.
Indicated for management of primary and secondary symptoms of psychotic disorders. /Thioxanthenes; Included in US product labeling/

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Drug Warnings
CHLORPROTHIXENE IS CONTRAINDICATED IN PATIENTS WHO ARE HYPERSENSITIVE TO THE DRUG; THE POSSIBILITY OF CROSS-SENSITIVITY TO PHENOTHIAZINES & TO THIOTHIXENE MUST BE BORNE IN MIND.
CHLORPROTHIXENE IS CONTRAINDICATED IN PATIENTS WITH CIRCULATORY COLLAPSE & IN THOSE WITH CONGESTIVE FAILURE, CARDIAC DECOMPENSATION, CORONARY ARTERY, OR CEREBRAL VASCULAR DISORDERS.
CHLORPROTHIXENE IS CONTRAINDICATED IN COMATOSE STATES, PARTICULARLY THOSE INDUCED BY CNS DEPRESSANT DRUGS.
WHEN CHLORPROTHIXENE IS USED CONCOMITANTLY WITH OTHER CNS DEPRESSANTS, CAUTION MUST BE OBSERVED TO AVOID OVERDOSAGE...
For more Drug Warnings (Complete) data for CHLORPROTHIXENE (27 total), please visit the HSDB record page.

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Pharmacodynamics
Chlorprothixene is a typical antipsychotic drug of the thioxanthine class. It has a low antipsychotic potency (half to 2/3 of chlorpromazine). Chlorprothixene has not thoroughly demonstrated an antidepressant or analgesic effect but it has demonstrated antiemetic effects. It is used in the treatment of nervous, mental, and emotional conditions. Improvement in such conditions is thought to result from the effect of the medicine on nerve pathways in specific areas of the brain. Chlorprothixene has a similar side effect profile to chlorpromazine, though allergic side effects and liver damage are less frequent.

C18H18CLNS

315.86

315.084

C, 68.45; H, 5.74; Cl, 11.22; N, 4.43; S, 10.15

113-59-7

Chlorprothixene hydrochloride; 6469-93-8

667467

Light yellow to khaki solid powder

1.3±0.1 g/cm3

435.0±45.0 °C at 760 mmHg

97-98°

216.9±28.7 °C

0.0±1.0 mmHg at 25°C

1.683

6.05

28.54

0

2

3

21

381

0

ClC1C([H])=C([H])C2=C(C=1[H])/C(=C(\[H])/C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])/C1=C([H])C([H])=C([H])C([H])=C1S2

WSPOMRSOLSGNFJ-AUWJEWJLSA-N

InChI=1S/C18H18ClNS/c1-20(2)11-5-7-14-15-6-3-4-8-17(15)21-18-10-9-13(19)12-16(14)18/h3-4,6-10,12H,5,11H2,1-2H3/b14-7-

(3Z)-3-(2-chlorothioxanthen-9-ylidene)-N,N-dimethylpropan-1-amine;hydrochloride

2934.99.03.00

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (7.91 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 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；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: ≥ 2.5 mg/mL (7.91 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 25.0 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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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。