Smooth muscle sensitization and neuromuscular depression induced by chronic administration of antimalarial drugs.

The functional effects on chick smooth and skeletal muscle of chronic administration of 60 mg kg-1 chloroquine or quinacrine given as daily intraperitoneal injections for 70 days have been investigated. Noradrenaline and potassium chloride (KCl) contracted the normal expansor secundariorum muscle, a smooth muscle from the wing of chicks wholly innervated by noradrenergic nerves. The muscle was unresponsive to acetylcholine and histamine. Chronic administration of chloroquine or quinacrine induced supersensitivity of expansor muscles to KCl and the muscles were contracted by acetylcholine and histamine. These actions were more pronounced in quinacrine-treated chicks and could be due to direct smooth muscle sensitization that may result in postjunctional changes. The oesophagus is a smooth muscle that is predominantly under parasympathetic control. The oesophagus from chronically-treated chicks was more sensitive to acetylcholine and KCl than the control muscles. This sensitization was more marked for chloroquine than quinacrine. Chronic administration of chloroquine and quinacrine depressed skeletal muscle contractions evoked by acetylcholine and potassium chloride. These findings indicate that chronic chloroquine and quinacrine administration sensitise smooth muscle to agonist drugs but depress neuromuscular transmission.