Pyrrolizidine alkaloids: actions on muscarinic receptors in the guinea-pig ileum.

1. Eleven pyrrolizidine alkaloids have been tested on the isolated guinea-pig ileum preparation.2. Platyphylline, supinine, heleurine and cynaustraline were more potent in antagonizing responses to acetylcholine and carbachol than responses to histamine. Their anticholinergic activity appeared to involve a competitive mechanism.3. Lasiocarpine, monocrotaline, spectabiline, sarracine, 7-angelylheliotridine, heliotrine and senecionine had similar antagonistic potencies against responses to both acetylcholine and histamine.4. The alkaloids had no appreciable activity as antagonists of acetylcholine in the isolated toad rectus abdominis preparation.5. These results are discussed with respect to interactions of the alkaloids at receptor sites involved in anticholinergic activity at the muscarinic receptor.