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Bipiperidyl mustard, a new obesifying agent in the mouse
Abstract:
Bipiperidyl mustard, after conversion to its bis-cyclic immonium ion forme, has been found to cause rapid and extensive lipid deposition in mice given single doses of the drug. The obe sity appears to result from an alkylation reaction; the responses of the treated ani mals to food restriction and realimenta tion resemble those observed in gold thioglucose-treated mice; also in anal ogy to gold thioglucose, the bipiperidyl mustard effects can be counteracted by sulfhydryl compounds. These observa tions are suggestive of a similarity of mode of action between the alkylating agent and gold thioglucose, a conclusion which is supported by preliminary find ings of ventromedial lesions in the hypo thalamus of the bipiperidyl mustard treated mice.
Insights
Bipiperidyl mustard induces rapid lipid deposition and obesity in mice via an alkylation mechanism. Its effects, similar to gold thioglucose, can be reversed by sulfhydryl compounds and involve hypothalamic lesions.
Area of Science:
- Pharmacology
- Neuroscience
- Biochemistry
Background:
- Bipiperidyl mustard is an alkylating agent.
- Obesity is a complex metabolic disorder.
- Gold thioglucose is known to induce obesity via hypothalamic lesions.
Purpose of the Study:
- To investigate the effects of bipiperidyl mustard on lipid deposition and obesity in mice.
- To explore the mechanism of action of bipiperidyl mustard.
- To compare the effects of bipiperidyl mustard with gold thioglucose.
Main Methods:
- Single-dose administration of bipiperidyl mustard to mice.
- Observation of lipid deposition and body weight changes.
- Assessment of responses to food restriction and refeeding.
- Administration of sulfhydryl compounds as a counteraction.
- Preliminary histological examination of hypothalamic lesions.
Main Results:
- Bipiperidyl mustard caused rapid and extensive lipid deposition, leading to obesity.
- The drug's effects were counteracted by sulfhydryl compounds.
- Responses to dietary manipulations mimicked those seen with gold thioglucose.
- Preliminary findings indicated ventromedial hypothalamic lesions in treated mice.
Conclusions:
- Bipiperidyl mustard induces obesity through an alkylation reaction.
- The mechanism of action shares similarities with gold thioglucose.
- Hypothalamic ventromedial lesions are implicated in bipiperidyl mustard-induced obesity.