Effect of phenoxybenzamine on neural and humoral control of sweat glands.

It is evident that the role of phenoxybenzamine as an alpha adrenergic blocking agent is suspect in the sense that it, in concert with some other alpha adrenergic blocking agents, may display a low degree of specificity." 2 Other alpha adrenergic blocking agents the specificity of which has been questioned include bretylium and guanethidine. They have been described as exerting, in doses of from 10 to 30 times that for adrenergic nerve blockade, a curarelike (which is to say, an antinicotinic) action in cholinergic systems.3' 4 These latter two agents, considered by some as seemingly less controversial than phenoxybenzamine, will be discussed in a subsequent paper.' In the meanwhile, and for present purposes, it is well to bear in mind that controversy exists concerning phenoxybenzamine. The reasons for using alpha adrenergic blocking agents in connection with studyof transmission to, and chemical action on, sweat glands are simple. Cholinergic innervation of the sweat glands is established beyond peradventure.6 And yet the glands respond by secretion to injected noradrenaline, the action not being blocked by atropine, the anticholinergic (muscarinic) blocking agent that is so effective in blocking action by sudomotor impulses, injected acetylcholine, and injected pilocarpine.7 8 An account of events leading to the foregoing statement is given in reference 9. Granting, as one must, that noradrenaline acts, the problem is to attempt evaluation of its role, if any, in neuroglandular transmission. It is to this end that alpha adrenergic blocking agents have been employed. In commenting on their study of the cholinergic blocking action of antiadrenergic agents, Boyd et al."0 stress their view that "the use of autonomic drugs as analytical tools is not reliable unless combined with both histochemical examination of the preparation and assay of the substances released upon stimulation of the nerves." This is more easily said than done. In fact, the last-mentioned condition for reliability, at least insofar as the sweat glands are concerned, seemingly is a priori impossible, for inextricably intermeshed with the sweat glands are other structures, adrenergically innervated, that could with equal justification be designated the origins of released adrenergic transmitter, supposing this were to be recovered for assay. Such a problem did not face Dale and Feldberg in establishing acetylcholine as the/a transmitter to sweat glands.6 If, then, one accepts the strictures of Boyd et al.,'0 it follows that the observations in this and subsequent papers on adrenergic blocking agents cannot be construed as constituting irrefutable evidence for an adrenergic step in the sudomotor innervation of sweat glands. Nevertheless, the question of such a step in sweat gland innervation is raised and must be considered a possible, even possibly a probable, aspect of the largely confused general picture of autonomic transmission and