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Biomedical subjects

M F Sugrue

Publications and source records attributed to M F Sugrue.

At least 55 records · Page 3Linked to original sources
PubMed1980

The inability of chronic mianserin to block central alpha 2-adrenoceptors.

An investigation was undertaken of the effect of long-term mianserin administration on the clonidine-induced decrease in rat brain MHPG-SO4 content. The dose of clonidine (0.1 mg/kg) chosen was one considered to selectively activate central alpha 2-adrenoceptors. Mianserin (10 mg/kg) given once daily for 9 and 15 days failed to alter the response to clonidine. This contrasts with the observations that acute and 5 day mianserin treatment blocks the clonidine-induced reduction in rat brain MHPG-SO4 levels. The possibility of mianersin-induced changes in the sensitivity of alpha 2-adrenoceptors is discussed. Chronic mianserin administration was associated with elevated levels of MHPG-SO4. This may have resulted from blockade of alpha 1-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1979

On the role of 5-hydroxytryptamine in drug-induced antinociception.

1. The effects of four specific inhibitors of 5-hydroxytryptamine (K-HT) uptake on morphine-, methadone- or pethidine-induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55 degrees C) reaction times. The effect of the compounds on the uptake of [3H]-5-HT into rat whole brain synaptosomes was also investigated. 2. Pretreatment with Org 6582, citalopram, zimelidine or femoxetine at doses devoid of antinociceptive activity potentiated morphine- but not methadone- or pethidine-induced antinociception. 3. A temporal correlation existed between the ability of Org 6582 to potentiate morphine-induced antinociception and to block synaptosomal [3H]-5-HT uptake. 4. 5-HT plays a critical role in the antinociceptive effect of morphine but not of methadone or pethidine.

Analgesics↗
PubMed1977

Some effects of mazindol, an anorectic drug, on rat brain monoaminergic systems.

Mazindol was devoid of effect both on rat brain steady state levels of 5-HT, 5-HIAA and tryptophan and on the rate of synthesis of 5-HT in the rat brain. Mazindol had no effect on rat brain 5-HT uptake in vivo as determined by the effect of drug pretreatment on the ability of p-chloroamphetamine to lower central 5-HT levels. A large dose of mazindol caused a slight transient decrease in rat brain levels of NA and DA. Blockade of rat brain catecholamine uptake was quantified by studying drug effects on the ability of intraventricularly administered 6-hydroxydopamine to lower brain NA and DA content. Mazindol was an extremely potent inhibitor of rat brain NA uptake in vivo, being 4-5 times more potent than desipramine. Mazindol also blocked rat brain DA uptake. Doses of mazindol needed to release alpha-methyl-m-tyramine from the rat striatum were appreciably greater than the corresponding doses of d-amphetamine. The neurochemical profile of mazindol bears a much closer resemblance to that of d-amphetamine than to that of fenfluramine.

Animals↗
PubMed1977

Effects of mianserin, a new antidepressant, on the in vitro and in vivo uptake of monoamines.

1 The effects of mianserin and of selected tricyclic antidepressants were compared in a number of monoamine uptake models. 2 The ability of mianserin to block the noradrenergic neurone membrane amine pump of rabbit brain stem slices was comparable to that of imipramine and amitriptyline and less than that of desipramine and nortriptyline. Both mianserin and desipramine were competitive inhibitors of noradrenaline uptake in vitro. The effect of mianserin on noradrenaline uptake in vivo was studied both peripherally and centrally. The ability of 6-hydroxydopamine to lower rat heart noradrenaline levels was found to be very sensitive to inhibition by tricyclic antidepressants. Mianserin was active in this model. However, its ability to block the 6-hydroxydopamine-induced fall in rat heart noradrenaline concentration was appreciably less than that of the tricyclics studied. 3 Mianserin, like tricyclic antidepressants, was essentially devoid of effect on dopamine uptake both in vitro and in vivo. 4 The ability of mianserin to inhibit [3H]-5-hydroxytryptamine uptake by rat hypothalamic synaptosomes was appreciably less than that of the tricyclic antidepressants studied. Mianserin was essentially devoid of effect on rat brain 5-hydroxytryptamine uptake in vivo. 5 It is concluded that in certain situations large doses of mianserin may block noradrenaline uptake in vivo. However, in no way does mianserin rival tricyclic antidepressants in blocking monoamine uptake in vivo. The clinical efficacy of mianserin cannot be attributed to inhibition of monoamine uptake.

Animals↗
PubMed1976

On the selective inhibition of serotonin uptake in vivo by Org 6582.

In vivo blockade of 5-HT uptake was studied by investigating the effect of drug pretreatment on the ability of p-chloramphetamine to lower rat brain 5-HT levels. Org 6582 was approximately twice as potent as fluoxetine, five times more potent than chlorimipramine and 14 times more potent than desipramine in blocking the ability of p-chloroamphetamine to lower rat brain 5-HT content. Org 6582 also had a longer duration of action than either fluoxetine or chlorimipramine. Org 6582, whilst having no effect on amine steady state levels, decreased rat brain 5-HT turnover and also lowered rat brain levels of 5-HIAA. In contrast to both desipramine and chlorimipramine, Org 6582 was devoid of effect on the ability of 1-metaraminol and 6-hydroxydopamine to lower rat heart NA levels. The ability of intraventricularly administered 6-hydroxydopamine to lower rat brain NA levels was unaltered by Org 6582 pretreatment. The corresponding i.p. ED50 values for desipramine and chlorimipramine were 7.3 mg/kg and 28.8 mg/kg respectively. Like desipramine and chlorimipramine, Org 6582 had no effect on the ability of intraventricular 6-hydroxydopamine to lower rat brain DA content. Org 6582 had no effect on steady state levels or on the turnover of NA and DA in the rat brain. It is concluded that Org 6582 is a potent long acting selective inhibitor of 5-HT uptake in vivo.

Animals↗