MMB4 DMS: cardiovascular and pulmonary effects on dogs and neurobehavioral effects on rats.
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.
Battelle, 505 King Avenue, Columbus, OH 43201, USA. rocheb@battelle.org
Brian M
BM
Roche
Tom M
TM
Vinci
Michael A
MA
Hawk
Craig R
CR
Hassler
David T
DT
Pressburger
Merrill R
MR
Osheroff
Glenn D
GD
Ritchie
Brian L
BL
Burback
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*
D000931:Antidotes; D010091:Oximes; C005514:N,N'-monomethylenebis(pyridiniumaldoxime)
MMB4; cardiovascular toxicity; neurobehavioral toxicity; pulmonary toxicity; safety pharmacology