Effects of pirenzepine (Gastrozepin) on skeletal muscle contractility

The effects of pirenzepine (Gastrozepin), a new anti-ulcer drug, on skeletal muscle contractility and on neuromuscular transmission have been examined in some experimental models in vitro and in vivo. Pirenzepine (5-500 micrograms/ml) inhibited agonist-(acetylcholine-, carbachol- or nicotine-) induced contractions of the toad isolated rectus abdominis muscle, and depressed electrically provoked twitches of the rat phrenic nerve-hemidiaphragm muscle preparation in vitro. Pirenzepine (5-25 mg/kg i.v.) also depressed indirect electrical stimulation-evoked twitches of the cat tibialis anterior and soleus muscle preparations in vivo. The neuromuscular blockade elicited by the anti-ulcer drug was not reversed by physostigmine, which reversed the depressant effects of d-tubocurarine on the electrically induced muscle twitches. Pirenzepine potentiated the depressant effects of d-tubocurarine on electrically evoked twitches of all skeletal muscles examined, and caused 'recurarisation' of partially curarised muscles. While the clinical significance of the neuromuscular blockade produced by the anti-ulcer agent is highlighted, it is concluded that the mechanism of skeletal muscle paralysing action of pirenzepine still remains speculative.