Chlorpromazine hydrochloride

Chlorpromazine Hydrochloride is an antagonist of the dopamine D2, 5HT2A, potassium channel andsodium channel. Chlorpromazine binds with D2 and 5HT2A with Kis of 363 nM and 8.3 nM, respectively.

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Neurological Disease

Ki: 363 nM (dopamine D2 receptor), 8.3 nM (5-HT2A receptor)[4]

Chlorpromazine (3, 10, 20, 40, and 60 μM) decreases the peak currents of hNav1.7 in a concentration-dependent manner, with IC50 of 25.9 μM with a Hill coefficient of 2.3. Chlorpromazine (25 μM) produces strong use-dependent inhibition of the hNav1.7 current. Chlorpromazine blocks the hNav1.7 channel, independent of calmodulin[1]. Chlorpromazine blocks HERG potassium channels with an IC50 value of 21.6 μM and a Hill coefficient of 1.11. Chlorpromazine (1, 10, 100 μM) blocks HERG potassium channels expressed in Xenopus laevis oocytes in a concentration-dependent manner. Chlorpromazine blocks HERG potassium channels in the activated state[5].

Chlorpromazine (2 mg/kg, i.p.)-induced neurobehavioural abnormalities (NAs) are characterized by significant increase in cataleptic behaviour and loared spontaneous activity reaction time in mice[2]. Chlorpromazine (1 or 5 mg/kg, i,p.) prevents ketamine (KET) from increasing average spectral power of delta and gamma-high bands on the 5th and 10th days of treatment in rats[3].

Adult mice (8-10 weeks old) weighing 18-25 g are divided into five groups of six mice per group. The treatment schedule is as follows: Group 1, control (Normal Saline: NS, 10 mL/kg i.p.); Group 2, chlorpromazine (CPZ, 2 mg/kg i.p.); Group 3, bromocriptine (BMC, 2.5 mg/kg s.c.); Group 4: amlodipine (AML, 1 mg/kg s.c.); Group 5, BMC (2.5 mg/kg s.c.) + AML (1 mg/kg). Animal treated with BMC or AML or their combination also receive chlorpromazine 30 min later (i.p.). Animals are subjected to various tests including metal bar test for catalepsy and spontaneous activity wheel for motor assessment and agility and elevated plus maze, hole-board, Y-maze, open-field tests for locomotory activity, and exploratory behaviour respectively. Animals are euthanized eighteen hours later by cervical dislocation. The brain is dissected, rinsed in buffer (pH 7.6) and homogenized with Teflon and used for assessment of lipid peroxidation, reduced glutathione, superoxide dismutase and catalase.

[1]. Lee SJ, et al. Mechanism of inhibition by chlorpromazine of the human pain threshold sodium channel, Nav1.7. Neurosci Lett. 2017 Feb 3;639:1-7

[2]. Kale OE, et al. Amlodipine, an L-type calcium channel blocker, protects against chlorpromazine-induced neurobehavioural deficits in mice. Fundam Clin Pharmacol. 2017 Jan 19

[3]. Sampaio LR, et al. Electroencephalographic study of chlorpromazine alone or combined with alpha-lipoic acid in a model of schizophrenia induced by ketamine in rats. J Psychiatr Res. 2017 Mar;86:73-82

[4]. Suzuki H, et al. Comparison of the anti-dopamine D? and anti-serotonin 5-HT(2A) activities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof. J Psychopharmacol. 2013 Apr;27(4):396-400

[5]. Thomas, D., et al. The antipsychotic drug chlorpromazine inhibits HERG potassium channels. Br J Pharmacol, 2003. 139(3): p. 567-74.

Nigericin sodium salt | Senicapoc | EIPA | Harmine | E-4031 | 4-AMINOPYRIDINE | CB-154 mesylate | Pimavanserin | SCH 23390 hydrochloride | Levodopa | Riluzole | Cabergoline | Ginsenoside Rg3 | TRAM-34 | Serotonin hydrochloride

MOLECULAR FORMULA :

C17-H19-Cl-N2-S.Cl-H

MOLECULAR WEIGHT :

355.35

WISWESSER LINE NOTATION :

T C666 BN ISJ B3N1&1 EG &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

6071 ug/kg

TOXIC EFFECTS :

Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

18 mg/kg

TOXIC EFFECTS :

Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

6 mg/kg

TOXIC EFFECTS :

Behavioral - anorexia (human) Gastrointestinal - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

35 gm/kg/16Y-I

TOXIC EFFECTS :

Behavioral - rigidity (including catalepsy) Cardiac - pulse rate increase, without fall in BP Lungs, Thorax, or Respiration - respiratory stimulation

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

1786 ug/kg/2D-I

TOXIC EFFECTS :

Behavioral - irritability Lungs, Thorax, or Respiration - respiratory stimulation Skin and Appendages - sweating

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

822 ug/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - excitement Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

145 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LC50 - Lethal concentration, 50 percent kill

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

40 mg/m3/2H

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

62 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

25 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

90 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

135 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - rigidity (including catalepsy) Behavioral - alteration of classical conditioning

TYPE OF TEST :

LC50 - Lethal concentration, 50 percent kill

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

40 mg/m3/2H

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

92200 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

420 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

>30 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - muscle weakness Behavioral - rigidity (including catalepsy)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

5 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

109 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

420 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Bird - chicken

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Bird - chicken

DOSE/DURATION :

28 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

900 mg/kg/30D-I

TOXIC EFFECTS :

Related to Chronic Data - changes in ovarian weight Related to Chronic Data - changes in uterine weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

50 mg/kg/5D-I

TOXIC EFFECTS :

Related to Chronic Data - changes in ovarian weight Related to Chronic Data - changes in uterine weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

300 mg/kg

SEX/DURATION :

female 6-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

50 mg/kg

SEX/DURATION :

female 7-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

250 mg/kg

SEX/DURATION :

female 7-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

350 mg/kg

SEX/DURATION :

female 7-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1980 mg/kg

SEX/DURATION :

male 4 week(s) pre-mating female 4 week(s) pre-mating - 3 week(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2500 ug/kg

SEX/DURATION :

male 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

25 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

100 mg/kg

SEX/DURATION :

female 14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

100 mg/kg

SEX/DURATION :

female 14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - gastrointestinal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

50 mg/kg

SEX/DURATION :

female 12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

12 mg/kg

SEX/DURATION :

female 12-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

24 mg/kg

SEX/DURATION :

female 17-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - postpartum Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

12 mg/kg

SEX/DURATION :

female 12-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

24 mg/kg

SEX/DURATION :

female 17-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

125 mg/kg

SEX/DURATION :

male 5 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

300 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

300 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

150 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

21 mg/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

10 mg/kg

SEX/DURATION :

female 3 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - other effects to embryo

MUTATION DATA

TEST SYSTEM :

Rodent - rat

DOSE/DURATION :

25 mg/kg

REFERENCE :

DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 9,41,1986 *** REVIEWS *** TOXICOLOGY REVIEW JMSCA9 Journal of Mental Science. (London, UK) V.4-108, 1857-1962. For publisher information, see BJPYAJ. Volume(issue)/page/year: 106,755,1960 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - M1050 No. of Facilities: 830 (estimated) No. of Industries: 2 No. of Occupations: 3 No. of Employees: 905 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - M1050 No. of Facilities: 188 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 3661 (estimated) No. of Female Employees: 1936 (estimated)