Transmission and block in autonomic ganglia / by W.D.M. Paton.

  • Paton, William D. M.
Date:
[1954?]
Catalogue details

Licence: In copyright

Credit: Transmission and block in autonomic ganglia / by W.D.M. Paton. Source: Wellcome Collection.

    5/10 (page 63)
    63 esterases. Thus Feldberg and V artiainen (14) required special conditions of submaxima] stimulation before they could demonstrate, with eserine an effect on normal transmission. Chou and Elio (9) were able to show a moderate antago¬ nism to d-tubocurarine by carefully chosen doses of eserine, provided brief peno s of stimulation were used, but none with neostigmine. Grob and Harvey ’ m man, could not antagonise the hypotension produced by C6 with neo- s igmine. n my own experience, an antagonism to hexamethonium in animals can sometimes be shown, but not invariably. It cannot be argued that this is because anticholinesterases themselves readily produce a block which ‘neutral- ises as it were, the looked-for augmentor or antagonistic action. For this too is quite hard to produce and is, indeed, only well seen in the perfused ganglion All this is m considerable contrast to the neuromuscular junction at which anti¬ cholinesterases produce a wealth of effects: such as vigorous repetitive discharge . Sln§e shocks with,potentiation of the twitch, an antagonism to curare-like drugs which the veriest tyro can be sure to demonstrate, and a block with repeti¬ tive stimulation so considerable as to lead, in early work, to the belief that they were preimanly depressant to transmission. The usefulness of the anti-curare effect of antiesterases at the neuromuscular junction receives almost its strongest testimony m its widespread employment clinically; but these agents have no -orrespon ing use against ganglionic block, a striking fact even when allowance S rmi the 1ther dmgS avaiIable as antidotes which act directly on effector Is. W hi e it is by no means true to say, therefore, that anticholinesterases are active on the neuromuscular junction and not at the ganglion, it does appear that heir actions are much more prominent at the former than at the latter. .,Slng,a,.drug suoh as d-tubocurarine, there is a certain variation in the sensi- lvity of different muscles. But this variation is not great; from the account of xpenments such as that by Smith et al (23) it seems that a four-fold increase in ose m the numan will carry you from the early stages of block of the most msitive muscles to virtually complete paralysis. With ganglia on the other hand ns oes not seem to be the case. Even within a single ganglion, the superior rvica ganglion of the cat, one needs about ten times as much hexamethonium paralyse the contraction of the nictitating membrane as to paralyse dilatation the pupil. Salivary secretion in the cat is particularly sensitive and begins to be ected by a dose one-five hundredth of that needed completely to paralyse the e superior cervical ganglion. Similarly in man, some subjects will respond by a 11 of blood pressure to as little as 1 to 5 mg. hexamethonium, although in others ceiving amounts of 1 gm. or more per day, evidence of incomplete ganglionic ock can be obtained. Lntil interest arose m synthetic curarizing compounds and later in ganglion DC mg substances, the fact that the blocking agents normally used were active °th synapses, obscured differences between them in their specific affinities, ut now that the synthetic chemists have irrupted into pharmacology, destroy - g o d ideas and bringing a wealth of new ones, there are countless examples of ugs significantly more active on one synapse or the other, among derivatives natural alkaloids as well as in wholly synthetic products. A particularly