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Biomedical subjects

A Uzan

Publications and source records attributed to A Uzan.

At least 109 records · Page 6Linked to original sources
PubMed1979

Study of two new non-steroid anti-inflammatory drugs having a pyrazole structure (LM 22070 and LM 22102).

Two derivatives from a new heteroarylacetic series, 1,3,4-triphenylpyrazole-5-acetic acid (LM 22102) and 1-isobutyl-3,4-diphenylpyrazole-5-acetic acid (LM 22070), were selected on the basis of their anti-inflammatory, analgesic and antipyretic properties. In the mouse, LM 22102 and LM 22070 were respectively 15 and 30 times less active than indomethacin in Koster's test, but they were 9 and 13 times less toxic than the reference drugs. In contrast, they were very active in the rat and the guinea-pig. LM 22102 appeared to be as active as indomethacin in the various tests performed: Randall and Selitto's test for analgesic activity, hyperthermic rat, experimental models of inflammation (UV erythema, carrageenin-induced oedema, cotton granuloma, adjuvant-induced arthritis). In vitro, its inhibition of prostaglandin-synthetase in guinea-pig lung was appreciably more powerful than that of indomethacin. Like all potent non-steroid anti-inflammatory drugs it has ulcerogenic activity, similar to that of indomethacin, which accounts for its acute oral toxicity in the rat. The activity of LM 22070 is either the same as (antipyretic action) or inferior to (analgesic and anti-inflammatory activity and inhibition of prostaglandin-synthetase) that of indomethacin, but always markedly superior to that of phenylbutazone. Its ulcerogenic activity and oral acute toxicity in the rat are respectively 2.5 and 3 times weaker than those of indomethacin.

Animals↗
PubMed1979

Relationships between plasma corticosteroids and benzodiazepines in stress.

Forcing a rat to swim in a situation from which there is no escape results in an increase in plasma corticosteroid level. This rise was selectively inhibited by benzodiazepines, phenobarbital and meprobamate but not by other psychotropic drugs like trycyclic antidepressants, monoamine oxidase inhibitors, neuroleptics and amphetamines. This effect of benzodiazepines is of central origin since diazepam did not block the rise in plasma corticosteroid level produced by adrenocorticotrophic hormone. Diazepam also had no effect on plasma corticosteroid levels in hypophysectomized rats or in rats treated with betamethasone. Brief stress did not alter binding of [3H]diazepam in vitro nor binding of [3H]flunitrazepam in vivo.

Adrenal Cortex Hormones↗
PubMed1979

The antithrombotic activity of viquidil, a cerebral vasodilator.

1-(6-Methoxy-4-quinolyl)-3-(3-vinyl-4-piperidyl)-1-propanone (viquidil, Desclidium) when administered parenterally was a potent inhibitor of thrombus formation in the microvasculature of the hamster cheek pouch. The drug was active at a minimum dose level of approximately 2.5 X 10(-4) mg/kg and appeared to be more potent than papaverine in the same test system. Papaverine was shown to be toxic at higher dose levels with intermittent vasodilatation and haemorrhage. Viquidil, however, appeared to be approximately twice as potent as papaverine and was apparently without toxic side-effects.

Animals↗
PubMed1976

[Absorption, distribution and excretion of (quinuclidinyl-3 methyl)-10-phenothiazine (LM 209), a new antihistamine].

1. The absorption, distribution and elimination of 10-(3-quinuclidinylmethyl)-phenothiazine (LM 209) were studied in the rat and dog after oral or intravenous administration of the 35S-labelled molecule. 2. Determinations of radioactivity in the rat and dog confirmed absorption and showed that the blood levels increase in proportion to the dose but remain very low compared with tissue concentrations. These were highest in the liver and lung and persisted at high level for more than 6 h after dosage. 3. Excretion of radioactivity was by the urinary and faecal routes. The high level of radioactivity in faeces resulted mainly from biliary excretion which was accompanied by much entero-hepatic circulation. 4. The prolonged retention of LM 209, due to binding to blood and tissue proteins and to entero-hepatic circulation, did not lead to noticeable accumulation of the drug after repeated doses. 5. The difference in the intracellular distribution of LM 209 and phenothiazine shows the importance of the quinuclidine N-subsitution on the phenothiazine ring, and results in a greater affinity to sub-cellular particulate fractions (nuclei, mitochondria, microsomes).

Animals↗
PubMed1976

[Biotransformation of 10-(3-quinuclidinylmethyl)phenothiazine (LM 209), a new anti-allergy agent and the distribution and excretion of its metabolites].

1. Metabolism of 10-(3-quinuclidinylmethyl)phenothiazine and the distribution and excretion of the metabolites, especially the sulphoxides, were studied in rat and dog after oral and intravenous administration. 2. Urine and bile contained relatively little unchanged drug. The sulphoxide, sulphone, N-oxide and N-oxide sulphoxide derivatives were identified as well as glucuronide and sulphate conjugates, suggesting the formation of hydroxylated products. Faeces contained mainly unchanged drug but also some sulphoxide and N-oxide. In the lung, brain and cerebro spinal fluid only unchanged drug and traces of sulphoxide were found, whereas in liver sulphone and N-oxide were also present. 3. After administration of the 35S-labelled sulphoxide, the distribution of radio-activity was very different from that observed with LM 209. The biological half-life (t0-5) of SM 209 was 3 to 4 times higher than that of the sulphoxide. LM 209 is better absorbed and its diffusion in the organism is superior. 4. Metabolism of LM 209 by liver microsome preparation was more rapid than metabolism of the sulphoxide. 5. These findings indicate that the activity of LM 209 is due more to the molecule itself than to its major metabolite.

Administration, Oral↗
PubMed1976

[Inhibition of 3', 5'-cyclic AMP phosphodiesterase in the guinea pig lung by a new anti-allergic: 10-(3-quinuclidinylmethyl) phenothiazine (LM 209)].

The action of a new antiallergic agent, 10-(3-quinuclidinylmethyl) phenothiazine or LM 209, on cAMP phosphodiesterase (PDE) was studied on a guinea-pig lung preparation and compared with that of other compounds such as cromoglycate (I), dexamethasone (II), dexchlorpheniramine (III), promethazine (IV) and theophylline (V). Compounds I, IV and V are competitive inhibitors whereas LM 209 and compound III are non competitive inhibitors of PDE. Compound II is practically inactive on the enzyme. Compounds III and V produce an inhibition of equal intensity, independently of the substrate concentration. Compounds I and IV are more active on PDE with low affinity than on PDE with strong affinity, whereas it is the contrary with LM 209. The mechanism of action of LM 209 at the pulmonary level is discussed in the light of these findings.

3',5'-Cyclic-AMP Phosphodiesterases↗