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Pharmacologic and toxicologic effects of di(beta-phenylisopropyl)amine (DPIA) in rats and mice
H Ketema1, W M Davis, L A Walker
1Department of Pharmacology, School of Pharmacy, University of Mississippi, University 38677.
Abstract:
1. Di(beta-phenylisopropyl)amine (DPIA) given i.p. to mice and rats in sublethal doses caused increased motility, mild stereotypic behavior and suppression of food intake. Repeated daily doses led to enhanced motor stimulation, and in one group, 40% lethality, indicating development of "reverse tolerance". Brain monoamine modifiers prevented DPIA-induced motor activity. 2. Treatment with toxic i.p. doses of DPIA enabled determination of the LD50, which was 106.8 mg/kg for isolated mice and 89.7 mg/kg for mice kept in aggregation after dosing. Possible antidotal agents given before a high DPIA dose (LD50) protected significantly against lethality. 3. Combinations of DPIA with (+)-amphetamine in mice at lethal doses showed a subadditive synergism. 4. Effects of DPIA on the cardiovascular system, both i.v. in anesthetized rats and in isolated atrial preparations, were mainly opposite to those of (+)-amphetamine, namely decreases in blood pressure, force of contraction and heart rate.
Insights
Di(beta-phenylisopropyl)amine (DPIA) causes motor stimulation and reverse tolerance in rodents. Antidotes protected against DPIA lethality, and its cardiovascular effects opposed those of amphetamine.
Area of Science:
- Neuropharmacology
- Toxicology
- Cardiovascular Pharmacology
Background:
- Di(beta-phenylisopropyl)amine (DPIA) is a compound with potential psychoactive properties.
- Understanding its effects on behavior and physiology is crucial for assessing its risks.
Purpose of the Study:
- To investigate the behavioral and physiological effects of DPIA in rodents.
- To determine the acute toxicity (LD50) of DPIA.
- To explore potential antidotal treatments and interactions with amphetamine.
- To characterize DPIA's impact on the cardiovascular system.
Main Methods:
- Sublethal and toxic doses of DPIA were administered intraperitoneally (i.p.) and intravenously (i.v.) to mice and rats.
- Behavioral observations included motility and stereotypic behavior.
- Lethality studies determined the LD50.
- Cardiovascular parameters were measured in anesthetized rats and isolated atrial preparations.
- Interactions with monoamine modifiers and (+)-amphetamine were assessed.
Main Results:
- Sublethal DPIA doses increased motility, induced stereotypic behavior, and suppressed food intake, with repeated doses leading to enhanced motor stimulation and
- reverse tolerance
- 40% lethality in one group.
- The LD50 was determined as 106.8 mg/kg (isolated mice) and 89.7 mg/kg (grouped mice).
- Antidotal agents significantly protected against DPIA-induced lethality.
- Combinations of DPIA and (+)-amphetamine showed subadditive synergism.
- DPIA's cardiovascular effects (decreased blood pressure, heart rate, and force of contraction) were largely opposite to (+)-amphetamine.
Conclusions:
- DPIA exhibits stimulant properties and can induce reverse tolerance in rodents.
- Effective antidotal agents exist for DPIA toxicity.
- DPIA interacts synergistically with amphetamine.
- DPIA possesses distinct cardiovascular effects compared to amphetamine.