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An important pharmacodynamic action of certain compounds known as “antihistaminic agents” is that of adrenergic potentiation. Ths feature has been demonstrated in reference to the adrenergic control of feline blood pressure, salivation and retraction of the nictitating membrane, and of canine blood pressure and intestinal motility.

1. The activities of a new antispasmodic, N, N-di-methylthymy loxyacetamidine hydrochloride and of its diethyl congener have been compared with the corresponding activities of Trasentine, Trasentine-6H, and atropine sulfate in respect to the following: a. Antagonism of a histamine-induced spasm of the ileum of the guinea pig. b. Antagonism of an acetylcholineinduced spasm of the ileum of the guinea pig. c. Antagonism, of a barium chloride-induced spasm of the small intestine of the rabbit. d. Actions on the feline uterus in vitro and in vivo. e. Actions on the nictitating membrane of the cat and on salivation induced by drugs and by stimulation of the chorda tympani nerve. f. Paralysis of the peripheral cut vagus in the cat. g. Antagonism of Mecholyl-induced hypotension in the cat. h. Intravenous LD50 in white rats. i. Chronic toxicological studies in dogs and rats. 2. The effects of Su-198 upon the intestines of dogs with Thiry-Vella loops and upon the bronchioles of the perfused guinea pig’s lung have been described. 3. Some of the problems have been discussed which must be solved before an objective evaluation of an antispasmodic becomes possible.

Summary and ConclusionsPriscol (benzylimidazoline) is sympatholytic as well as adrenolytic in reference to the sympathetic neural control of blood pressure and salivation. Adrenolysis invariably precedes sympatholysis with any dose that is adequate to produce both effects. These pharmacodynamic actions persist during priscol hypotension, pituitrin hypertension and in the presence of atropine.Although sympathetic depression of salivation and vasoconstriction can be produced with variable doses of priscol, up to 15 mg, they are without sympatholytic or adrenolytic effect upon the cervical sympathetic neural components controlling mydriasis, indicating that a differential sympathetic depression characterizes this antisympathetic agent.

Until approximately a decade ago a sympathetic blocking agent was little more than a scientific curiosity but today the picture has been con­ siderably altered; certain sympathetic blocking chemicals have come into their own as valuable therapeutic agents. They have become available to us through the fine cooperation of our research scientists, a group which includes the chemist, the biologist, and the clinical investigator. In the development of these important drugs as available to physicians today is the pharmacologist who early recognized, with the inquisitive clinician, the important role that sympathetic predominance plays in the symptomatology of certain disorders which reflect imbalance of the autonomic nervous system. Some of these include neurogenic hypertension, certain peripheral vascular diseases, especially Raynaud's and probably Buerger's disease, herpes zoster, hyperthyroidism, tachycardia, glaucoma, exophthalmia, migraine headaches (spastic type), neurodermatoses, renal hypertension (in part neurogenic in origin?), vasospastic dysmenorrhea, causalgia, and probably some types of epilepsy. There is little doubt today that the autonomic nervous system plays a very important role, either directly or indirectly in many diseases, in terms of overactivity or underactivity of either portion of the autonomic nervous system, that is, of the parasympathetic or the sympathetic divisions. Our attention at the moment is directed toward suppressing, within desirable physiologic limits, the overactivity of the sympathetic portion of this system in certain undesirable conditions. This goal can be achieved by cer­ tain recently developed chemical compounds which have already established their value as therapeutic agents. Inspection of Fig. 1, a diagram by Hafkenschie1 & Sellers (1), which is an excellent modification of that previously employed (2), reveals various focal points of attack in the establishing of sympathetic or adrenergic blockade. The synonymous or interchanging use of the terms sympathetic and adrener­ gic blockade, a procedure which will be followed throughout this presentation should be noted. Adrenergic refers to that portion of the autonomic nervous system, namely the sympathetic portion, which responds to the action of adrenaline or adrenaline-like substances. These include epinephrine and norepinephrine in particular; any agent that blocks these substances which act in the region of the final arborization or distribution of sympathetic nerve fibers, that is, within the receptive substance of the end organs asso­ ciated with sympathetic innervation, is classified as a sympathetic or adrenergic blocking agent. On the other hand, one must bear in mind that

1. A theoretical explanation for the epinephrine-fast state as a manifestation of imbalance in the histamine-sympathin see-saw is presented (“epinephrine-histamine toxicity”). The experimental observations described lead us to conclude that repeated administrations of epinephrine to such individuals produce an increase in plasma histamine overcoming the effects of the epinephrine. It is theoretically plausible that suitably administered antihistaminic agents might return the see-saw to its normal balance. 2. In eight of a group of ten patients displaying epinephrine-fastness significant improvement followed the use of intravenous tripelennamine hydrochloride or diphenhydramine hydrochloride. Epinephrine, administered subcutaneously or by the aerosol route, appeared to bring relief from acute paroxysmal bronchospasm, whereas previously only the side effects of epinephrine had been observed following its use.

Summary1. The hydrochloride salts of yohimbine derivatives (ethyl, allyl-amine, allyl, butyl, phenyl and diethylaminoethyl) in the dosage used, 1-500,000 to 1-50,000, do not seem to directly affect the arterial muscle strip whether it is in a contracted or relaxed state. 2. A predetermined, consistently constricting dose of epinephrine HC1, 1-1,000,000, or ephedrine, 1-25,000, administered after yohimbine derivatives is inhibited in its action. 3. This inhibitory action of the yohimbine radicle on epinephrine can be obviated by previously sensitizing the arterial strip to epinephrine by addition of cocaine. 4. Musculo-tropic agents such as histamine, 1-1,000,000, barium chloride, 1-1,000, and sodium nitrite, 1-1,000, are not modified in their actions by yohimbine derivatives. 5. These new yohimbine derivatives are antisympatheticomimetic agents.

ConclusionsThe compound 2-[N-p′-tolyl-N-(m′-hydroxyphenyl)-aminomethyl] -imidazoline HCl, (C-7337), is a potent adrenolytic agent but much less active as a symptatholytic drug. It is effective orally.6

The pharmacological effects of 1-hydrazinophthalatine (Ba-5968) have been reported. Its two principal actions were hypotension and partial adrenolysis. Doses of from 0.25 to 1.0 mg./Kg. intravenously usually sufficed in the dog and cat to produce the maximal hypotensive response that the drug could effect. Further marked increases in the dose exerted no obvious effect. The hypotensive action of the drug was characterized by a slow development of the maximal effect after a significant latent period. The action is probably central since the drug little influenced the blood pressure of “spinal” cats and dogs and did not affect the flow in the perfused vascular bed of the rabbit's hind limb. Both acute and chronic toxicological studies have evidenced the safety and high therapeutic index of the compound.

In the past one has been able to affect the autonomic nervous system to a varying degree in most respects except in depression of the sympathetic or adrenergic nervous system ; but the latter is now becoming a reality in certain respects. The problem of applying adrenergic blockade has been attacked and encouraging results have been obtained so that the medical profession can now treat the varied syndrome of sympathetic predominance. Vasospastic conditions of the vascular tree, including neurogenic or essential hypertension, are peculiarly susceptible in many instances to adrenergic blockade, and it behooves the medical profession to become more aware of the role of sympatholytics and the newer suppressants of sympathetic overflow.

Since Hughson and Scarff1 first reported peristaltic augmentation of the ileum after NaCl intravenously in anesthetized cats, several investigators have confirmed the observation.2, 3, 4, 5 Regarding the response of the colon no action has been experimentally demonstrated. Thus our results seem interesting since they show that the large intestine can be activated by salt solutions of adequate hypertonicity when intravenously administered.This work was carried out in unanesthetized, trained collies, which had undergone cecostomy after the method described by Plant and Miller.6 Rubber balloons of convenient size, under uniform water pressure were inserted into the anterior colon and registrations were recorded through a closed system6 by means of Mendenhall's7 modified Brodie8 bellows. Varying amounts, 2 to 15 cc., of NaCl 5% and 20% concentration were injected intravenously and intracardially.Results. 5% NaCl only slightly (a) augments colonic tonus, (b) increases peristaltic amplitude.5% NaCl does not alt...

The cathartic agent known as the A. B. & S. pill, even though relegated to the National Formulary, is still rather freely recommended by some practitioners and consequently is promiscuously used by the public. Hence there are frequent disastrous consequences when these pills are eaten by unsuspecting youngsters who presume that the beautifully colored and sugar-coated pellets are "candy" rather than "deadly buckshot" by virture of the contained strychnine which accompanies the belladonna and aloin. The danger of all disguised medicants containing strychnine is vividly portrayed by Aikman 1 in his analysis of agents responsible for death preceded by convulsions in children under 5 years of age. He finds that strychnine in the form of Hinckle's, A. B. & S., and A. B. S. & C. pills or tablets is the most frequent causative poisoning agent. In 1929 in Dr. O. H. Plant's laboratory at Iowa City, experiments 2 with

To the Editor:— You have frequently been the recipient of many excellent suggestions intended for general improvement of the medical and allied professions. Recently the recommendation to advocate universal adoption of the metric system in lieu of the apothecary system was given prominence and justifiably so. Can you listen to another? All too frequently authors of proposed publications in the medical sciences are confronted with varying whims and idiosyncrasies of editorial board members in relation not only to structure, content and style of presentation but in particular to one feature of a manuscript which should by all measures of practicability and convenience be uniform, namely the bibliographic notations. Your organization has made a real contribution in the direction of standardization in this situation, but spasmodic or rhythmic reference must apparently be indulged in until our editorial boards eventually see the "wisdom of (your) ways" and follow suit. If one chooses

To the Editor:— In the June 30, 1962, issue ofThe Journal( 180 :1106), there appears a special communication, "A Study of the German Outbreak of Phocomelia," by Helen B. Taussig, M.D., on which we would like to comment. This relates to the statement beginning on page 1108: "Thalidomide is a synthetic drug which, as the story is told in West Germany, was first conceived and made by Ciba and found by them to have no effect on animals;..." The story heard by Dr. Taussig is not accurate, since Ciba neither conceived nor made thalidomide and was never associated with its clinical investigation. Dr. Taussig has also commented briefly inThe Journalarticle, but more extensively in her testimony before the Celler Committee and in her article in the current issue of Scientific American , that glutethimide (Doriden) is similar in molecular structure to thalidomide. Attention is called to the formulae

Examines early views on the treatment of hypertension, factors underlying the development of hypertension, and the chemistry of hypertension drugs.

Excerpt The disadvantages attending therapeutic use of morphine and other analgetics have impelled investigators in numerous fields of medical endeavor to seek an adequate substitute for the relief...

To the Editor:— In Queries and Notes in a recent issue ofThe Journal(February 14, p. 567) one reads the reply to the disturbing question concerning the safe concentration of sodium sulfathiazole when used in medicating the nasal mucosa. As was so well stated, sodium sulfathiazole is not free of undesirable reactions because of the irritating properties associated with its alkalinity. Aqueous solutions of sodium sulfathiazole vary in p H from 10 to 11 and may become yellow on standing, especially when unprotected from daylight. To obviate the strong alkalinity, irritating properties and deterioration of such solutions, we have dissolved various sulfonamides in propylene glycol ( Modern Hospital 57 :106 [July] 1941; J. Indiana M. A. , to be published in April). The most useful of these propylene glycol preparations have been a 3 per cent solution of sulfathiazole, a 3 per cent solution of sulfapyridine and a 10 per cent