Related Experiment Video
Updated: May 9, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
MMB4 DMS: cardiovascular and pulmonary effects on dogs and neurobehavioral effects on rats
Brian M Roche1, Tom M Vinci, Michael A Hawk
1Battelle, 505 King Avenue, Columbus, OH 43201, USA. rocheb@battelle.org
Abstract:
The objectives of these studies were to determine the cardiopulmonary effects of a single intramuscular administration of 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) on dogs and on the central nervous system in rats. On days 1, 8, 15, and 22, male and female dogs received either vehicle (water for injection/0.5% benzyl alcohol/methane sulfonic acid) or MMB4 DMS (20, 50, or 100 mg/kg). Pulmonary function was evaluated for the first 5 hours after concurrent dosing with cardiovascular monitoring; then cardiovascular monitoring continued for 72 hours after dosing. Rats were dosed once by intramuscular injection with vehicle (water for injection/0.5% benzyl alcohol/methane sulfonic acid) or MMB4 DMS (60, 170, or 340 mg/kg). In dogs, 100 mg/kg MMB4 DMS resulted in increased blood pressure, slightly increased heart rate, slightly prolonged corrected QT, and moderately increased respiratory rate. There were no toxicological effects of MMB4 DMS on neurobehavioral function in rats administered up to 340 mg/kg MMB4 DMS.
Insights
1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) showed mild cardiopulmonary effects in dogs at high doses but no neurobehavioral toxicity in rats. This study assessed the safety of MMB4 DMS in preclinical models.
Area of Science:
- Pharmacology
- Toxicology
- Veterinary Medicine
Background:
- 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) is a compound requiring safety evaluation.
- Understanding its effects on cardiopulmonary and central nervous systems is crucial for potential applications.
Purpose of the Study:
- To investigate the cardiopulmonary effects of MMB4 DMS in dogs.
- To assess the central nervous system (CNS) effects and neurobehavioral toxicity of MMB4 DMS in rats.
Main Methods:
- Dogs received intramuscular injections of MMB4 DMS (20, 50, or 100 mg/kg) or vehicle, with pulmonary and cardiovascular monitoring for up to 72 hours.
- Rats received intramuscular injections of MMB4 DMS (60, 170, or 340 mg/kg) or vehicle, followed by neurobehavioral assessments.
Main Results:
- In dogs, the highest dose (100 mg/kg) of MMB4 DMS caused increased blood pressure, heart rate, corrected QT interval, and respiratory rate.
- No significant toxicological effects on neurobehavioral function were observed in rats even at the highest dose (340 mg/kg).
Conclusions:
- MMB4 DMS exhibits dose-dependent, mild cardiopulmonary effects in dogs.
- MMB4 DMS demonstrates a lack of neurobehavioral toxicity in rats, suggesting a potentially favorable safety profile for the central nervous system.
