Dose-Related Response of Mouse Mamma to Some Phenothiazine Drugs

Itoh, Tadanobu

doi:10.2131/jts.3.147

Cited by 3 publications

(2 citation statements)

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“…Observations of lethargy, rough coat, prostration, hypothermia, reduced food consumption, and decreased body weights in chlorpromazine-dosed mice in the current study have been observed in other studies in rodents (1,23,50). Findings of minimally higher serum glucose values, lymphopenia, and lymphoid atrophy in the spleen, thymus, and lymph nodes in the 4-week study in mice were compatible with a stress response.…”

Section: Discussionsupporting

confidence: 89%

“…The magnitude of the increase in blood prolactin levels was generally higher in females than males (3,4,25,31,42). Immature, ovariectomized mice administered a single subcutaneous dose of estradiol followed by 9 days of oral administration of a phenothiazine including chlorpromazine, exhibited a slight hypertrophy of the mammary gland at the end of dosing (23).…”

Section: Discussionmentioning

confidence: 98%

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Toxicity and Carcinogenicity Studies of Chlorpromazine Hydrochloride and p-Cresidine in the p53 Heterozygous Mouse Model

Petruska¹,

Frank²,

Freeman

et al. 2002

Toxicol Pathol

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The carcinogenic potential of chlorpromazine hydrochloride, a psychotropic agent, was assessed in the p53 heterozygous mouse assay. In a 4-week dose range finding study in p53 wild-type mice, doses of 20,40, 60, and 80 mg/kg were poorly tolerated because of mortality secondary to the severe sedative and hypotensive effects of chlorpromazine. Based on 40% mortality at a dose of 20 mg/kg in the dose-range finding study, a high dose of 10 mg/kg was chosen for the 26-week carcinogenicity study in p53 heterozygous mice. Doses of 2.5, 5, and 10 mg/kg chlorpromazine hydrochloride were well tolerated in the 26-week study. The administration of chlorpromazine hydrochloride at dose levels up to and including 10 mg/kg to p53 heterozygous and wild-type mice did not result in a dose-related increase in tumor incidence or in the type of tumors seen in comparison to controls. Findings related to the administration of chlorpromazine in the 26-week study were limited to minimal uterine and ovarian atrophy in p53 wild-type mice dosed with 10 mg/kg chlorpromazine hydrochloride. However, p53 heterozygous mice administered 400 mg/kg p-cresidine, a genotoxic carcinogen commonly used as a positive control for this model, developed urinary bladder tumors. Administration of p-cresidine also resulted in a regenerative anemia, splenic and hepatic hemosiderosis, renal findings, and ovarian and uterine atrophy. This study demonstrated that chlorpromazine hydrochloride, at the doses tolerated, was not carcinogenic in the p53 heterozygous mouse assay.

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Section: Discussionsupporting

confidence: 89%