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The effects of adrenaline and isoprenaline on the tension and time-course of the contractions of the tibialis anterior and soleus muscles of cats and rabbits have been compared with the effects of previous high-frequency stimulation. Like a tetanus, adrenaline possessed a facilitating action on neuromuscular transmission and an action exerted directly on the muscle fibres. Isoprenaline possessed only the second of these two actions. The effect of adrenaline and isoprenaline on the muscle fibres was blocked by dichloroisoprenaline and by 1-(2 naphthyl)-2-isopropylaminoethanol, whereas the effect of adrenaline on neuromuscular transmission was blocked by phentolamine and by phenoxybenzamine. In the soleus muscle, both the catechol amines and a previous tetanus caused similar decreases in maximal twitch tension and in the times to peak tension and to half-relaxation. The muscle action potentials were unaltered or slightly increased in amplitude. In the tibialis anterior muscle, a previous tetanus and the catechol amines caused an increase in twitch tension and an increase in the overall duration of the twitch. The muscle action potentials were either unchanged or were slightly decreased in amplitude. In this muscle the effect of a tetanus differed from that of the catechol amines in that the large post-tetanic change was associated with a marked increase in the rate of rise of twitch tension.Adrenaline and some other sympathomimetic amines have been shown to increase the maximal twitch tension of unfatigued fast-contracting skeletal muscles in various mammalian species

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A new class of antimuscarinic drugs was designed and synthesized. The compounds are "soft" quaternary ammonium esters in which there is only one carbon atom separating the ester oxygen and the quaternary head. The compounds are potent anticholinergics when derived from hindered "umbrella" acids and cholinergics when derivatives of simple aliphatic acids. The more potent anticholinergics have up to 10 times higher acetylcholine antagonist activity than atropine, but they have a much shorter duration of action. The compounds cleave hydrolytically with simultaneous destruction of the quaternary head. The compounds are promising as selective, local agents, particularly as inhibitors of eccrine sweating.

1(-)-Isoprenaline and the selective P1-adrenoceptor agonist R0363 were tested for their inotropic effects in left atrial (1i,) 3 The pKD values for (-)-isoprenaline were similar in the two tissues (left atria 6.4, uterus 6.0) whilst for R0363 the atrial value (7.8) was considerably greater than that for the uterus (6.0). The latter value is very similar to the pKB value determined from shifts in (-)-isoprenaline curves produced by R0363 in uterine preparations. 4 Graphical plots of the fraction of receptors occupied vs response were constructed. The relative efficacy of (-)-isoprenaline with respect to R0363 was calculated to be 25 in atrial and 2633 in uterine preparations.5 The selective Pf-adrenoceptor stimulant actions of R0363 are a reflection of both its greater affinity and efficacy for Pl-as opposed to P2-adrenoceptor sites. The potent actions of (-)-isoprenaline in both tissues are largely dependent on efficacy.