ISSN:0031-7012    

DOI:10.1159/000135585

出版商:S. Karger AG    

年代:1965

数据来源: Karger

摘要:

The various effects of histamine on smooth muscles and other tissues are thought to be mediated by two pharmacologically distinct receptors, Ht and H2 types. These receptors are defined in terms of their susceptibility to blockade by pyrilamine (typeíi!) or burimamide (typeH2). In this study selective antagonism of the spasmodic effects of histamine on isolated strips of rabbit detrusor has shown that the response is mediated by H1 receptors, with no evidence of H2 activity. The pA2 of the pyrilamine-histamine antagonism is 9.3. The histamine response is susceptible to muscarinic blockade (atropine and propantheline) but not to nicotinic blockade (hexamethonium). Adrenergic blocking agents propranolol (10–4M) and phenoxybenzamine (10–8M) do antagonize the contractile response, but this does not appear to be indicative of adrenergic media

ISSN:0031-7012    

DOI:10.1159/000136879

出版商:S. Karger AG    

年代:1975

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135586

出版商:S. Karger AG    

年代:1965

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135587

出版商:S. Karger AG    

年代:1965

数据来源: Karger

摘要:

The effect of fenfluramine, administered orally in a daily dose of 1 mg/kg for 40 days, on the disposition and rate of elimination of antipyrine was studied in 15 obese patients. Although the plasma half-life of antipyrine was unchanged, the apparent volume of distribution (1/kg) fell by 11.6 % (p < 0.001) and the plasma metabolic clearance rate (1/kg/h) of antipyrine was reduced by 14.1 % (p < 0.01). No correlation occurred between change in clearance, on the one hand, and change in patient weight or apparent volume of distribution of antipyrine, on the other. In vitro drug-metabolizing enzyme activity in the rat was measured using rate of aminopyrine and hexobarbital metabolism as indices. Fenfluramine inhibited the metabolism of both substrates. It is concluded that fenfluramine can diminish the rate of elimination of drugs which are extensively metabolized by reduction of microsomal enzyme activity. Also, drug clearance may be diminished by reduction of apparent volume of distribution.

ISSN:0031-7012    

DOI:10.1159/000136880

出版商:S. Karger AG    

年代:1975

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135588

出版商:S. Karger AG    

年代:1965

数据来源: Karger

摘要:

Sensitivity of the central nervous system (CNS) to the hypnotic effect of hexobarbital was assessed by analytical, pharmacokinetic, and electroencephalographic techniques in male and female rats and in mice of both sexes by the first two techniques. These experimentally and conceptually diverse measures yielded strikingly similar estimates of CNS sensitivity to hexobarbital which was independent of both species and sex, while well known species and sex (rat) differences in duration of response to hexobarbital were demonstrated.

ISSN:0031-7012    

DOI:10.1159/000136881

出版商:S. Karger AG    

年代:1975

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135589

出版商:S. Karger AG    

年代:1965

数据来源: Karger

摘要:

Contrasting with the hypertension resulting consistently after DOCA implantation, mature female rats given Enovid daily for 20 weeks had only slight and occasional increases in blood pressure. The pressure elevations remained infrequent and transient even when drinking water was replaced with isotonic saline solution but they became more pronounced when Enovid treatment was initiated at an earlier age. Despite the failure to cause sustained hypertension, the data indicate that Enovid affects blood pressure and that both mestranol and norethynodrel are essential for this effect. Pressor responses to norepinephrine or angiotensin were unaffected even after 20 weeks of pretreatment but those to electrical stimulation of the posterior hypothalamus were increased in rats pretreated with Enovid. Enhanced responsiveness to hypothalamic stimulation occurred only in the awake state and was not demonstrable after the central nervous system (CNS) had been depressed with urethane. These results can be explained by an increased sensitivity of hypothalamic pressor areas produced by Enovid prior to the development of hypertension and the mechanisms involved may be similar to those occurring in spontaneously-hypertensive rats. However, the possibility of hypersensitivity at other sites in the sympathetic vasomotor outflow cannot be ruled out.

ISSN:0031-7012    

DOI:10.1159/000136882

出版商:S. Karger AG    

年代:1975

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000135590

出版商:S. Karger AG    

年代:1965

数据来源: Karger