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D R Mottram

Publications and source records attributed to D R Mottram.

At least 37 records · Page 2Linked to original sources
PubMed1981

Differential blockade of pre- and postsynaptic alpha-adrenoceptors by the 2-R and 2-S enantiomers of WB4101.

Agonists and antagonists of the alpha-adrenoceptor have been shown to possess different degrees of potency at the pre- and postsynaptic levels. The present investigation was undertaken to see whether the two optical isomers of WB4101 likewise exhibit differential blockade at the two receptor sites. This was achieved by measuring the potencies of 2-R and 2-S WB4101 against noradrenaline-induced contractions of the rat isolated vas deferens and against clonidine-induced inhibition of the twitch response in field stimulated rat vas deferens. Results showed that though the enantiomers exhibited widely differing potency, as indicated by calculations of pA2 values, at the postsynaptic level, they possessed almost identical potency presynaptically. In addition, 2-aminomethyl-1,4-benzodioxan itself both exhibited reasonable presynaptic alpha-adrenoceptor blocking activity, whilst being devoid of activity postsynaptically. The values for slope on the Schild plots for 2-R and 2-S WB4101 indicated that they produced classical competitive antagonism at the postsynaptic receptor but at the presynaptic level the values for slope were indicative of a non-competitive type of blockade. Results are discussed in terms of recent suggestions of that agonists and antagonists of the alpha-adrenoceptor may not share a common mechanism or site of action at the presynaptic level.

Adrenergic alpha-Antagonists↗
PubMed1979

Potentiation of the response of rat vas deferens to noradrenaline by dicylohexylamine and related amines.

The results of a previous study on protection by propranolol and dicyclohexylamine of alpha-blockade suggested that these compounds potentiated the response of the isolated rat vas deferens to noradrenaline. A number of structural analogues of dicyclohexylamine (DCHA) have now been investigated for their effects on noradrenaline responses and some of them have been shown to potentiate these responses. At concentrations approaching those necessary to achieve maximum potentiation they also brought about the spiked contraction of the vas deferens. The potentiating effects of these amines are discussed together with their relevance to the protection of alpha-blockade.

Adrenergic beta-Antagonists↗
PubMed1979

Studies on the modes of action of dicyclohexylamine and related amines with a potentiating effect on noradrenaline responses in the rat vas deferens.

Previous studies have shown that dicyclohexylamine (DCHA) and related amines with saturated and unsaturated cyclic side-chains produce a potentiation of noradrenaline responses in rat vas deferens. The present study shows that the potentiation is mediated via a cocaine-like effect, by acting as neuronal uptake inhibitors on sympathetic nerve terminals of the rat vas deferens. Furthermore, it has been established that the contractions of the vas, which are induced by high concentrations of DCHA and its analogues, are due to an indirect sympathomimetic activity of these compounds.

Animals↗
PubMed1977

The sympathomimetic activity of fenfluramine hydrochloride on rat vas deferens.

1. The peripheral, pharmacological effects of the anorexigenic agent, fenfluramine hydrochloride, have been investigated on rat isolated vas deferens. 2. Characteristic spiked contractions were observed within 2 to 3 min after exposure to fenfluramine; these contractions reached a rate of around 13 per min and were of variable height. 3. Pre-treatment of vasa with the indirectly acting sympathomimetic amine, tyramine, greatly reduced both the height and rate of contraction induced by fenfluramine. 4. The uptake inhibitor, desipramine, required a concentration in excess of 10 micronM to affect fenfluramine-induced contractions. Effects of desipramine on fenfluramine contractions were of equal magnitude whether desipramine was administered before fenfluramine or at the height of the fenfluramine-induced contractions. 5. Pre-treatment with debrisoquine (0.5 mM), reduced the contractions in response to fenfluramine over a period of time. 6. Fenfluramine, added to vasa from rats which had been injected intraperitoneally with 5 mg/kg reserpine 24 h and 48 h previously, failed to induce its characteristic contractions. 7. It is concluded that fenfluramine can be classed as an indirectly acting sympathomimetic amine on peripheral adrenergic nerve terminals.

Animals↗
PubMed1977

Comparative study of propranolol and dicyclohexylamine protection of alpha-receptor blockade.

During the course of a study into protection against alpha-receptor blockade, it was observed that the dicyclohexylamine (DCHA) salt of 5-hydroxyindole acetic acid exhibited protection, whilst the free acid did not protect against alpha-receptor blockade. A study has been made into the protection of alpha-receptor blockade by DCHA and this compared with the beta-blocker propranolol, with which DCHA may share some structural similarity. It was also observed that at higher concentrations DCHA itself produced spiked contractions of the vas deferens. These properties of DCHA and their interrelationships with those of propranolol are discussed.

Animals↗
PubMed1976

Peripheral effects of fenfluramine.

1 The peripheral cardiovascular effects of the centrally acting anorexigenic agent, fenfluramine hydrochloride, have been investigated in the rat. 2 After intravenous administration of fenfluramine, an immediate hypotensive response, followed by a reflex rise in blood pressure was recorded. This was followed by a prolonged fall in blood pressure which frequently failed to return to pre-drug levels. 3 The antagonists, propranolol and atropine, failed to inhibit this hypotensive effect of fenfluramine. 4 The effects of 5 mg/kg fenfluramine for 1h on the blood pressure responses to the sympathomimetic amines, tyramine, methoxamine and metaraminol were studied. 5 The responses to the indirectly acting tyramine were reduced by 50% following fenfluramine, while those to the directly acting methoxamine remained unaffected by the drug. Responses to metaraminol, an amine with both direct and indirect actions, were also unaffected to a significant degree by fenfluramine. 6 Studies on rat isolated vas deferens again showed that responses to tyramine are greatly reduced following fenfluramine. 7 In addition fenfluramine itself produced spontaneous contractions of the vas deferens. These contractions were blocked by the alpha-adrenoceptor blocking agents phentolamine and thymoxamine. 8 It is suggested that fenfluramine exerts an effect at the adrenergic nerve terminal, either by displacing noradrenaline stores or by inhibition of the amine uptake process.

Amines↗