The Effect of Propranolol and Other Antagonists on Ciclazindol-Induced Glucose Uptake Into the Isolated Rat Hemidiaphragm

Acute dexfenfluramine administration normalizes glucose tolerance in rats with insulin‐deficient diabetes

“…Both dexfenfluramine and D,L-fenfluramine have been shown to increase glucose uptake into skeletal muscle and adipose tissue in uiuo in subjects with NIDDM [4-61, and some in uitro studies have demonstrated that fenfluramine enhances glucose uptake into isolated rat muscle, as long as some insulin is present [16]. Both dexfenfluramine and D,L-fenfluramine have been shown to increase glucose uptake into skeletal muscle and adipose tissue in uiuo in subjects with NIDDM [4-61, and some in uitro studies have demonstrated that fenfluramine enhances glucose uptake into isolated rat muscle, as long as some insulin is present [16].…”

“…In this study as in others [3,6], acute dexfenfluramine administration did not increase plasma insulin concentrations, and so probably improved glucose tolerance by enhancing or mimicking insulin action. Both dexfenfluramine and D,L-fenfluramine have been shown to increase glucose uptake into skeletal muscle and adipose tissue in uiuo in subjects with NIDDM [4-61, and some in uitro studies have demonstrated that fenfluramine enhances glucose uptake into isolated rat muscle, as long as some insulin is present [16]. Studies in fat-fed, insulin-resistant rats further suggest that dexfenfluramine also inhibits production of glucose by the liver, which is a major determinant of basal blood glucose concentrations [8].…”

Ciclazindol and mazindol on glucose uptake into human isolated skeletal muscle: no interaction of mazindol with methysergide.

“…Table 2 shows that the group of fenfluramine, norfenfluramine, S422 and flutiorex all require the presence of added insulin to produce a maximum effect, and that the effect of fenfluramine is inhibited by methysergide in therapeutic concentrations (Kirby & Turner, 1976b). Ciclazindol and mazindol on the other hand, do not require the addition of insulin, and the action of mazindol is not reduced by methysergide.…”

“…This has now been investigated further in two ways; firstly, ciclazindol (10-(m-chlorphenyl)-2,3,4,10-tetrahydropyrimido (1,2-a) indol-10-ol hydrochloride), a compound structurally related to mazindol (Figure 1) has been studied on this experimental preparation. Secondly, the effect of methysergide on the glucose uptake by mazindol has been studied as Kirby & Turner (1976b) have shown that the effect of fenfluramine is inhibited by this 5-hydroxytryptamine antagonist. …”

A new weight-reducing drug with novel properties

“…Ciclazindol is a member of the pyrimido 1 ,2oc-indol group of drugs and has a chemical resemblance to mazindol, a compound with established weight-reducing properties (General Practitioner Research Group 1978). Mazindol increases glucose uptake into human isolated skeletal muscle (Kirby & Turner, 1976) as does fenfluramine, another well established weight-reducing drug (Kirby, 1974) in contrast to amphetamine which has no such effect (Kirby and Turner, 1974). Kirby and Turner (1977) have shown that ciclazindol, like mazindol, produces a significant concentrationdependent increase in glucose uptake into human skeletal muscle.…”