RESUMO
Motor transmission in the guinea-pig vas deferens has been shown to be readily inhibited by adrenergic neuron blocking agents (Boyd, Chang & Rand, 1961; Bently, 1965) but Ambache & Zar (1971) found it to be resistant to O-adrenoceptor blocking drugs. They suggested that the motor transmission may not be adrenergic and they pointed out that the actions of the adrenergic neuron blocking agents may be unspecific and possibly associated with their local anaesthetic effect. I have estimated the motor transmission blocking activities of guanethidine, bretylium, pronethalol, propranolol and procaine and compared the results with their published local anaesthetic activities, in order to determine whether these two properties were potency-related. The vas deferns removed from Wistar rats (250-300 g) was cleared of mesenteric attachments, cut longitudinally and suspended under a tension of 1 g, in a 10 ml organ bath of McEwan solution (McEwan, 1956) at 35§. The solution was gassed with oxygen containing 5 percent carbon dioxide. The preparation was field stimulated by patinum electrodes at a frequency of 6Hz with rectangular pulses of 0.5 ms at supramaximal voltage (25 V). Muscular contractions were recorded isometrically by a force transducer (Grass FTO3C). The reduction in the height of the electrically induced twitches was measured 3 min after adding the drug. Two or three doses of each drug which produced between 30 and 80 percent inhibition of twitches were selected. The log dose-effect lines for the percentage inhibition of the electrically induced twitches of the isolated vas deferens by the drugs (are shown on a graph). Taking procaine as unity, the approximate relative potency was guanethidine 460, bretylium 70, pronethalol 6 and propranolol 5. In confirmatory experiments with the rabbit isolated innervated jejunum preparation (Finkleman, 1930), the drugs had the same relative order of potency in inhibiting the pendular movement induced by periaterial nerve stimulation. The order of potency of the drugs in inhibiting the electrically induced twitches of the rat vas deferens guanethidine > bretylium > pronethalol > propranolol > procaine. On the other hand, the order of local anaesthetic potency of the drugs is known to be propranolol > pronethalol > procaine > bretylium > guanethidine (Morales-Aguilera & Vaughan Williams, 1965; Gill & Vaughan Williams, 1964; Papp & Vaughan Williams, 1969; Davis, 1970; Bein, 1960). There was thus no correlation of local anaesthetic and motor transmission blocking activities, since guanethidine and bretylium, the least potent local anaesthetics, were the most potent inhibitors of responses to electrical stimulation. It does not seem reasonable, therefore, to attribute the blockade of the electrically induced twitches of the vas by the adrenergic neuron blocking agents directly to their trivial local anaesthetic action (AU)
