Actions of tetrahydropapaveroline on the cardiovascular system and skeletal muscles of the anaesthetized cat and on guinea-pig soleus muscle in vitro.

1. Tetrahydropapaveroline (THP) and isoprenaline have been compared for effects on heart rate, diastolic blood pressure and contractions of soleus and tibialis muscles in chloralose-anaesthetized cats and on in vitro guinea-pig soleus muscles. 2. All effects of THP were similar to those of isoprenaline. Maximal responses were the same and responses to both drugs were antagonized by propranolol. 3. THP produced an increase in heart rate, a fall in diastolic blood pressure and a decrease in the tension and degree of fusion of incomplete tetanic contractions of the soleus, being, respectively, 12.9, 14.7 and 19.6 times less potent than isoprenaline. The similarity in potency ratios suggests that THP is a non-selective beta-adrenoceptor agonist. 4. Effects on the guinea-pig soleus in vitro were similar to those in the cat soleus. 5. In the cat, THP enhanced the tension and duration of tibialis twitches, but the tibialis was about ten times less sensitive than the soleus to the effects of THP. 6. THP deepened neuromuscular blockade in partially curarized cat soleus and tibialis preparations. Doses required were ten times greater than for direct depressant effects on the soleus. 7. Agents which depress the tension and fusion of incomplete tetanic contractions of the cat soleus via beta-adrenoceptor stimulation cause tremor in man by peripheral effects on slow muscle fibres. THP is likely to exert such actions. This may explain why levodopa (a precursor of THP) sometimes precipitates a tremor crisis in Parkinsoniam patients, and why Parkinsonian tremor is relatively refractory to levodopa therapy. In such patients combination therapy with levodopa and a peripheral dopa decarboxylase inhibi;or (to reduce levels of THP) or a beta-adrenoceptor antagonist (to block the effects of THP on slow muscle fibres) could be advantageous.