Actions of chloroquine and its N-oxidation metabolites on the rectus abdominis muscle of the toad (Bufo regularis).

Using the isolate rectus abdominis muscle preparation of the toad (Bufo regularis) the pharmacological actions of chloroquine, chloroquine-N-oxide and chloroquine N-di-oxide were investigated. On their own at concentrations ranging from 7.5 x 10(-5) -5 x 10(-3)M, the compounds induced contractures, chloroquine being the most active. At lower concentrations (5 x 10(-7) - 5 x 10(-5) M), chloroquine and its N-oxides enhanced acetylcholine-induced contractures whereas they depressed the carbachol-evoked contractures. At higher concentrations (5 x 10(-4) - 5 x 10(-3)M), chloroquine and its N-oxides inhibited both ACh- and carbachol-induced contractures. Analysis of the results obtained showed that the antagonism between ACh (or carbachol) and chloroquine (or its N-oxides) is non-competitive. At low concentrations chloroquine and its N-oxides (5 x 10(-7) - 5 x 10(-5)M) inhibited the potentiating action of neostigimine on ACh-induced contractures. From the results obtained in the study presented here, it is suggested that the antagonism of acetylcholine (or carbachol) by chloroquine and its N-oxidation metabolites on this muscle preparation may be at the cellular level. It is also suggested that the compounds examined may be acting as anticholinesterases (with chloroquine being the most active).