Desipramine hydrochloride

Desipramine hydrochloride is an inhibitor of norepinephrine transporter (NET), 5-HT transporter (SERT) and dopamine transporter (DAT) with Kis of 4, 61 and 78,720 nM, respectively.

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

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

Signaling Pathways >> Neuronal Signaling >> Dopamine Transporter

Research Areas >> Neurological Disease

Ki: 4 nM (NET), 61 nM (SERT), 78720 nM (DAT)[1]

Treatment of rats with Desipramine hydrochloride for 14 days reduces norepinephrine transporter (NET) expression in a dose-dependent manner, as indicated by a reduction of the specific binding of 3H-nisoxetine to the NET in preparations of cerebral cortex (F(3,16)=4.33, p<0.05) and hippocampus (F(3,16)=4.34, p<0.05). This NET down regulation is observed 2 days after discontinuation of chronic Desipramine hydrochloride treatment, a time when plasma and brain concentrations of Desipramine hydrochloride and desmethyldesipramine are undetectable (ie below the 25 ng detection limit of the assay)[2].

Rats are anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg) and implanted subcutaneously with osmotic minipumps preloaded with either vehicle (50% saline, 40% DMSO, and 10% ethanol) or Desipramine hydrochloride at a concentration that delivered 5, 10, or 15 mg/kg per day of the free base. Minipumps are removed, under anesthesia, 14 days later. Rats are tested for antidepressant-like behavior in the forced-swim test 2 to 8 days after pump removal and discontinuation of Desipramine hydrochloride treatment. Following the completion of the behavioral tests, rats are killed by decapitation, their brains are removed, and cerebral cortex and hippocampus are dissected for neurochemical analyses[2].

[1]. Torres GE, et al. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 2003 Jan;4(1):13-25.

[2]. Zhao Z, et al. Norepinephrine transporter regulation mediates the long-term behavioral effects of the antidepressant desipramine. Neuropsychopharmacology. 2008 Dec;33(13):3190-200.

Harmine | Pimavanserin | Serotonin hydrochloride | Vanoxerine dihydrochloride | Sodium Ferulate | Thioridazine hydrochloride | Brexpiprazole | Risperidone | TG6-10-1 | Cariprazine | Fipexide | Quetiapine | SERTINDOLE | Alprenolol hydrochloride | B-HT 920

MOLECULAR FORMULA :

C18-H22-N2.Cl-H

MOLECULAR WEIGHT :

302.88

WISWESSER LINE NOTATION :

T C676 BN&T&J B3M1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

45 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - acute pulmonary edema

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

36 mg/kg/6D-I

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - hallucinations, distorted perceptions Gastrointestinal - decreased motility or constipation

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

5 mg/kg/5D-I

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Behavioral - toxic psychosis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

70 mg/kg/4W-I

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Behavioral - toxic psychosis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

490 ug/kg

TOXIC EFFECTS :

Behavioral - sleep

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

14 mg/kg/1W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - urine volume decreased Nutritional and Gross Metabolic - changes in sodium Nutritional and Gross Metabolic - changes in chlorine

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

871 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 - rat

DOSE/DURATION :

55 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 :

19 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 :

315 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 - mouse

DOSE/DURATION :

88 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 :

37 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - rigidity (including catalepsy) Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

25 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 :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

55 mg/kg

TOXIC EFFECTS :

Cardiac - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

130 mg/kg

SEX/DURATION :

female 10-22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

90 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

TYPE OF TEST :

Specific locus test

MUTATION DATA

TEST SYSTEM :

Insect - not otherwise specified

DOSE/DURATION :

10 gm/L

REFERENCE :

JCLBA3 Journal of Cell Biology. (Rockefeller Univ. Press, 1230 York Ave., New York, NY 10003) V.12- 1962- Volume(issue)/page/year: 47,182a,1970 *** REVIEWS *** TOXICOLOGY REVIEW IDPYAK Industrial Pharmacology. (Mount Kisco, NY) V.1-3, 1974-79. Discontinued. Volume(issue)/page/year: 2,209,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5341 No. of Facilities: 62 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 1952 (estimated) No. of Female Employees: 1089 (estimated)