Showing papers in "British journal of pharmacology and chemotherapy in 1956"

Studies on mammalian histidine decarboxylase.

Abstract: Histamine is present in most mammalian tissues, but its mode of formation is still not clear. According to Blaschko (1945) there are two main theories: (1) Histamine is a vitamin, formed outside the body by bacterial decarboxylation of dietary histidine in the alimentary tract. (2) Histamine is a metabolite, formed from circulating histidine by the histidine decarboxylase present in some tissues of the body. That bacteria form histamine by decarboxylation of histidine is well known (Ackermann, 1910, 1911; Berthelot and Bertrand, 1912; Mellanby and Twort, 1912; Kendall and Gebauer, 1930; Matsuda, 1933; Gale, 1940; Epps, 1945). Gale (1953) showed that the bacterial enzyme had several important differences from the other amino acid decarboxylases which had been studied. The occurrence of a mammalian histidine decarboxylase was demonstrated by Werle (1936) and by Holtz and Heise (1937a). They showed that, after rabbit kidney had been incubated with histidine in buffered Tyrode solution, histamine was present in the supernatant fluid obtained. Werle and coworkers (Werle, 1936, 1940, 1942; Werle and Herrmann, 1937; Werle and Krautzun, 1938; Werle and Heitzer, 1938; Werle and Daumer, 1940; Werle and Koch, 1949), together with Holtz and co-workers (Holtz and Heise, 1937a, 1937b; Holtz, Heise and Spreyer, 1938; Holtz, Credner and Reinhold, 1939; Holtz and Credner, 1941, 1944) carried out extensive investigations upon the distribution of this enzyme ill various tissues of different animal species and investigated many of its physical and chemical properties. They were unable to isolate the enzyme, though V\" erle and Heitzer (1938) claim to have achieved a partial purification. More recently, evidence of a mammalian histidine decarboxylase has been obtained by Schayer (1952), who injected guinea-pigs with 14C-labelled histidine and histamine. But these studies do not conclusively demonstrate the general

Some actions of chlorpromazine

Abstract: Since the first account of the pharmacology of chlorpromazine by Courvoisier, Fournel, Ducrot, Kolsky, and Koetschet (1953), much work has been done in an attempt to elucidate the mode of action of this drug. Investigations have been made by Bradley and Hance (1955), Dasgupta and Werner (1954), Hiebel, Bonvallet, and Dell (1954), Holzbauer and Vogt (1954), Longo, Von Berger, and Bovet (1954), Cathala and Pocidalo (1952), Huidobro (1954), Kopera and Armitage (1954), Melville (1954), Cosnier and Drouin (1954), Salzman, Moran, and Brodie (1955), and others. Chlorpromazine, like promethazine, is a phenothiazine derivative and possesses some of its actions to a greater degree, but it has negligible antihistamine properties. Perhaps the most outstanding property of chlorpromazine is its central depressant action, which is different from that of barbiturates, and is more marked than with other related phenothiazines. Its main peripheral action is an antagonism to adrenaline, and Kopera and Armitage (1954) showed that chlorpromazine also caused a paralysis of striated muscle. These authors compared the properties of chlorpromazine, promethazine, and pethidine, and found that all three substances showed the same types of pharmacological action, but chlorpromazine was the most active except in its anti-acetylcholine and antihistamine actions. In the present investigation we have determined pA2 values for the anti-acetylcholine and antihistamine properties of chlorpromazine. Its actions on striated muscle, on the heart for a quinidine-like effect, on body temperature, on insulin hypoglycaemia, and on liver glycogen, were also studied.