During the prodromal phase of a migraine attack, vasoconstriction occurs which is followed during headache by the dilatation of cranial blood vessels (Marcussen and Wolff, 1950). Therefore, the metabolism in migraine of physiologically occurring vasoactive substances such as 5-hydroxytryptamine (5HT) and the catecholamines is of interest. A further indication of the possible importance of 5HT is that ergot alkaloids, such as methysergide, used in the treatment of migraine are pharmacological antagonists of this substance. In particular, Sicuteri, Fanciullacci, Del Bianco, and Franchi (1964) find that methysergide prevents the venoconstrictive effect of 5HT. Sicuteri, Testi, and Anselmi (1961) have reported elevated 24-hour excretion of 5HIAA (the main urinary metabolite of 5HT) by some migraine patients on the days during which attacks occurred.Excretion of 3-methoxy-4-hydroxymandelic acid (V.M.A.), the main urinary metabolite of noradrenaline and adrenaline, has also been claimed by Sicuteri (1963) to be raised during attacks.Because of these observations, it was thought worthwhile to investigate 5HIAA excretion in migraine in greater detail, paying particular attention to the control of extraneous factors known to affect excretion of this substance. The excretions by some of the patients of another tryptophan metabolite, indoxyl sulphate, and of V.M.A. were also measured. MATERIALS PATIENTS The 13 patients studied in the main series of experiments included nine migraine subjects and four controls. The migraine subjects were subject to frequent attacks and admitted to hospital specifically for this reason, there being no evidence of any other organic disease. The control subjects were patients in a neurological hospital without demonstrable organic neurological disease or vascular or gastrointestinal disease. The patients cooperated actively in the study and filled in daily charts giving chronological and symptomatic details of their headaches. All patients were ambulant.Except where specifically stated otherwise, the normal hospital diet was used except that the following foods, which are known to contain 5HT in considerable amount, were excluded from the diet: bananas (Waalkes, Sjoerdsma, Creveling, Weissbach, and Udenfriend, 1958), pineapple (Bruce, 1960), walnuts (Kirberger and Braun, 1961), grapefruit and apricots (West, 1958). Alcohol was not allowed as it has been reported by Rosenfeld (1960) to influence 5HIAA excretion. Patients were taken off all drugs three days before the start of investigations. The daily fluid intake of each subject was controlled to a fixed volume.URINE COLLECTIONS Urine specimens were collected over four-hour periods for a varying number of days. Each specimen was collected into 1 ml. of 6N HCI, and on completion, placed in a cold room at 4°C. After measurement of volume, 50-100 ml. samples were stored at -25°C. until determinations were made. METHODS5HmiA An 1/80 sample of each four-hourly urine specimen was brought to 9 ml. with water and used for each determination, thus avo...

A series of 34 beta-arylamidoacrylic acids was prepared and examined for antiinflammatory activity. These compounds are vinylogous carbamic acids, and several displayed activity equal to phenylbutazone in the rat pleural effusion model. Highest activity was associated with structures bearing halogen and cyano substituents. Amides were inactive.

It has been reported that 3-substituted 2,4(1H,3H)quinazolinediones, particularly 3-[-(4-aryI-l-piperazinyl) alkyl ]-2,4 (1H ,3H)-quinazoliuediones,1 2 showed sedative and hypotensive activities in experimental animals. These findings led us to prepare analogous 2-substituted 2H-l,2,4-benzothiadiazin-3(4H)-one 1,1dioxides.3

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