摘要:

The molecules of thalidomide (I) and 3-azathalidomide (II) have the characteristic aromatic six-membered ring 1,2-dicarboximide structure which is regarded as necessary for effecting teratogenicity. Pregnant SWS mice were given single i.p. injections of I and II on day 9 of gestation. A mixture of physiological saline and Tween 20 (3:1) was used as solvent. II showed a much higher teratogenic and embryotoxic effect than I. This variation is assumed to be caused by a different ability of the two substances to intercalate between base pairs of the double helix of DNA.

ISSN:0031-7012    

DOI:10.1159/000136489

出版商:S. Karger AG    

年代:1974

数据来源: Karger

摘要:

Polymorphonuclear leukocytes of guinea pig were used to study the action of 5-hydroxytryptamine, histamine and methergoline on phagocytosis. Phagocytosis was reduced by 5-HT; this effect was only in part antagonized by histamine: the antagonism was not competitive. Methergoline at concentration higher than 1·10–6 reduced phagocytosis: this effect was not modified by histamine. At doses lower than 1 10–6 methergoline competitively antagonized the depression of phagocytosis caused by

ISSN:0031-7012    

DOI:10.1159/000136490

出版商:S. Karger AG    

年代:1974

数据来源: Karger

摘要:

The totally isolated canine stomach, perfused with homologous blood, was used to study the inhibitory action of metiamide, a histamine antagonist of the H2-blocking variety. Secretagogues, histamine or bethanechol chloride were infused separately or combined into the gastric artery for 6–7 h. When a basic secretion level was achieved after 2–3 h, metiamide was infused for 2 h, then infusion of secretagogue(s) continued for the remaining 2–3 h. Under all conditions of stimulation used in this study, metiamide significantly inhibited the concentration and output of HCl. In all stomachs studied there was a complete absence of titrable H+ at a certain stage of metiamide infusion or following such an infusion. These results indicate that the action of metiamide is not selectively limited to the antagonism of H2-receptors. Metiamide acts against both H2-receptors and muscarinic rece

ISSN:0031-7012    

DOI:10.1159/000136491

出版商:S. Karger AG    

年代:1974

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135481

出版商:S. Karger AG    

年代:1964

数据来源: Karger

摘要:

The antiphlogistic effect of topically applied anti-inflammatory drugs was studied on two experimental models of inflammation: the carrageenin-induced paw edema and the croton oil-induced ear edema. Etoclofene, the ethoxymethyl ester of N-(2,6 di-chloro-m-tolyl) anthranilic acid, showed to be as active as acetylsalicylic acid and phenyl-butazone in both tests. Meclofenamic acid, which is chemically very closely related to etoclofene, was less active than etoclofene on the croton oil-induced edema; while benzydamine was inactive in this test. Flufenamic acid and indomethacin showed a local anti-inflammatory activity lower than that of etoclofene on the carrageenin-induced paw edema. Etoclofene applied topically in combination with dexamethasone 17-valerate on edematous paws showed a small additive effect.

ISSN:0031-7012    

DOI:10.1159/000136492

出版商:S. Karger AG    

年代:1974

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135482

出版商:S. Karger AG    

年代:1964

数据来源: Karger

摘要:

(1) In the different vertebrates studied (mammals, amphibians, birds and fish) phenylbutazone, which was selected as a representative anti-inflammatory agent, was found to exert a varying degree of gastroulcerogenic activity. (2) The four anti-inflammatory agents, phenyl-butazone, oxyphenbutazone, indomethacin and flufenamic acid displayed a potent, acute ulcerogenic effect when administered orally to the rat. In the guinea pig and the mouse, a similar effect was only observed in response to higher (in some cases considerably higher) doses. (3) The margin between the median ulcerogenic and median lethal doses of phenylbutazone, oxyphenbutazone and flufenamic acid was narrow in the guinea pig and the mouse, but wide in the rat. In the case of indomethacin, it was wide in the mouse and narrow in the other two species. (4) The anti-inflammatory activity of the four preparations against acute oedema in the same species differed. (5) In the guinea pig, all four preparations showed a favourable therapeutic ratio, i.e. relation between anti-inflammatory and ulcerogenic activity; in the mouse and the rat, no consistent relationship was demonstrable. The most important finding emerging from these experiments is that ulcerogenicity and anti-inflammatory potency – in terms of the doses required to elicit these effects -need not necessarily parallel each othe

ISSN:0031-7012    

DOI:10.1159/000136493

出版商:S. Karger AG    

年代:1974

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135483

出版商:S. Karger AG    

年代:1964

数据来源: Karger

摘要:

The data reported demonstrate a synergistic response between the alkylating agents nitrogen mustard, cyclophosphamide, and thio-TEPA, and the barbiturate sodium pentobarbital. The synergistic toxicity found during the 24-hour observation period, occurred only when the alkylating agents were administered concomitantly with pentobarbital. For example, the LD50 of nitrogen mustard, cyclophosphamide, and thio-TEPA, determined in mice, 24-hour post-injection, was 24 mg/kg, 510 mg/kg and 400 mg/kg, respectively. When administered simultaneously with a non-lethal dose of 60 mg pentobarbital/kg, the LD50 of (a) nitrogen mustard, was reduced to 14.5 mg/kg; (b) cyclophosphamide, to 220 mg/kg and (c) thio-TEPA, to 250 mg/kg. Two alkylating agents displayed little (melphalan) or no (chlorambucil) enhanced toxicity for mice when given with pentobarbital. Atropine, 2 mg/kg, but not hexamethonium, 20 mg/kg, or decamethonium, 0.3 mg/kg, had definite palliative effects on the alkylating agent-pentobarbital interactions, thus suggesting a cholinergic mechanism for the synergies.

ISSN:0031-7012    

DOI:10.1159/000136494

出版商:S. Karger AG    

年代:1974

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135484

出版商:S. Karger AG    

年代:1964

数据来源: Karger