N-Benzyl-
N'N"-dimethylguanidine sulphate (BW 467C60) and its ortho-chloro derivative (
BW 392C60) had
adrenergic neurone blocking and
sympathomimetic effects resembling those of
bretylium and
guanethidine in cats, dogs and monkeys, but they were more potent in blocking
adrenergic mechanisms in the cat. BW 467C60 was more active than its chloro derivative. Each compound inhibited release of
noradrenaline during stimulation of the splenic nerve of cats, and increased smooth muscle responses to
adrenaline and
noradrenaline. Pressor responses to standard doses of
tyramine were also increased except when large doses of BW 467C60 or
BW 392C60 were given. The
adrenergic neurone block by BW 467C60 was inhibited by
dopamine,
cocaine and
amphetamine in situations in which these
amines inhibit the effects of
bretylium and
guanethidine. In contrast to
guanethidine, BW 467C60 and
BW 392C60 did not lower the pressor
amine content of the iris of cats 24 hr after administration of single doses of the compounds. BW 467C60 depressed the slope of curves relating the frequency of stimuli applied to the cervical sympathetic nerves and the resulting contraction of the nictitating membrane, but the effects of the lower rates of stimulation were preferentially inhibited. Large intravenous doses of BW 467C60 and
BW 392C60 blocked autonomic
cholinergic mechanisms and caused neuromuscular
paralysis of voluntary muscle. These effects were brief, in contrast to the
adrenergic neurone blockade. Both BW 467C60 and
BW 392C60 were well absorbed from the alimentary tract. In contrast to
guanethidine, BW 467C60 did not cause diarrhoea in guinea-pigs.