A comparison of the effects of repeated administration of cyclophosphamide, cytosine arabinoside or their combination on smooth and skeletal muscle.

The pharmacological effects of repeated administration of 2 mg Kg-1 cytosine arabinoside, 40 mg Kg-1 cyclophosphamide or their combination, all given once weekly for 5 weeks, have been investigated in chicks. Cyclophosphamide did not affect responses to noradrenergic nerve stimulation or phenylephrine, depressed responses of the expansor secundariorum muscle to acetylcholine but sensitised the muscle to direct stimulation. Cytosine arabinoside depressed noradrenergic transmission and enhanced responses of the expansor muscle to phenylephrine and acetylcholine. The combination of both drugs enhanced responses to noradrenergic nerve stimulation due to increased alpha-adrenergic receptor mediated contraction and direct muscle sensitisation. Cyclophosphamide, cytosine arabinoside or their combination produced a non-specific depression of the upper oesophagus and ileum. The exception was the marked increase in response of the ileum from the combination group to agonist drugs, indicating synergism. The non-specific skeletal muscle depressant actions of cyclophosphamide and the combination groups were more pronounced than that of the cytosine arabinoside group.