Donetidine

This study was designed to establish whether SK&F 93574 releases histamine in dogs. Three female beagle dogs each received single infusions (on separate days) of each of SK&F 93574 (2·5 mg kg−1), polyvinylpyrrolidone (PVP, 20 mg kg−1) and sterile saline. The treatments were given at 14 day intervals by rapid intravenous infusion at 0·5 mL kg−1 min−1 for 2 minutes. Dogs showed clinical signs of histamine release such as vasodilation, licking lips, head drooping and increased gut movement after treatment with the known histamine releaser PVP or the test compound SK&F 93574. These signs were of similar severity and duration for the two compounds. No such changes were observed when the dogs received vehicle alone. Treatment with PVP or SK&F 93574 also resulted in markedly elevated plasma histamine concentrations (> 10-fold increase over control). It is concluded that intravenous administration of SK&F 93574 to dogs is associated with histamine release.