Oxaprotiline: Induction of central noradrenergic subsensitivity by its (+)-enantiomer

Mishra, R.; Gillespie, David D.; Lovell, Richard; Robson, Ronald D.; Sulser, Fridolin

doi:10.1016/0024-3205(82)90309-5

Cited by 32 publications

(6 citation statements)

References 12 publications

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“…We found an increase in plasma melatonin concentrations throughout treatment with the active NA uptake blocker, ( + )oxaprotiline, which was not present during treatment with the inactive, in this respect, enantiomer, ( -)oxaprotiline. The effects of acute treatment with ( + )oxaprotiline are in keeping with previous studies of the effect of this drug and the somewhat less selective (Mishra et al 1982) but equally potent (Richelson, 1984) NA uptake inhibitor, desipramine Cowen et al 1985). First, the pharmacokinetics of the two enantiomers should be considered.…”

Section: Discussionsupporting

confidence: 66%

The acute and chronic effects of (+) and (−) oxaprotiline upon melatonin secretion in normal subjects

et al. 1992

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SYNOPSISTen healthy male subjects were treated for three weeks with (+)oxaprotiline, a selective inhibitor of noradrenaline (NA) uptake and with (−)oxaprotiline which does not inhibit NA uptake. Plasma melatonin concentrations were measured throughout the night at 0, 1, 7 and 21 days and were higher during treatment with (+)oxaprotiline than with (−)oxaprotiline for the entire three weeks of treatment. Since NA stimulates the production and secretion of melatonin, these results are consistent with a sustained increase in noradrenergic activity within the pineal, during 21 days of treatment with an effective NA uptake inhibitor.

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Section: Discussionsupporting

confidence: 66%

The acute and chronic effects of (+) and (−) oxaprotiline upon melatonin secretion in normal subjects

et al. 1992

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“…In contrast, chronic treatment with either (+)-or (-)-oxaprotiline did not alter the steady-state levels of GR mRNA (Fig. Importantly, we have previously demonstrated that (+)-oxaprotiline and DMI -in the doses used in the present studies and administered for seven days -were equipotent in reducing the sensitivity of the beta adrenoceptor coupled adenylate cyclase system to NE in brain and in down-regulating the density of beta adrenoceptors while (-)-oxaprotiline did as expected, not modify these two noradrenergic parameters (Mishra et al, 1982). Though one would not have expected the (-) enantiomer of oxaprotiline to alter hippocampal mRNA levels, if the synaptic availability of NE is a prerequisite for the activity of DMI, (+)-oxaprotiline should mimic the activity of DMI as the NE uptake blocking properties and the consequences on the NE beta adrenoceptor coupled adenylate cyclase system are equal to those of DMI (Delini-Stula et al, 1982;Mishra et al, 1982;Waldmeier et al, 1982).…”

Section: Resultssupporting

confidence: 79%

“…The (-)-enantiomer of oxaprotiline is devoid of these actions (Mishra et al, 1982;Delini-Stula et al, 1982). (+)-Oxaprotiline like DMI, is a potent inhibitor of the reuptake of NE thus increasing the synaptic availability of the catecholamine.…”

Section: Introductionmentioning

confidence: 99%

Increased synaptic availability of norepinephrine following desipramine is not essential for increases in GR mRNA

Eiring

Sulser

1997

J. Neural Transmission

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Male Sprague-Dawley rats were treated for 7 days with the norepinephrine (NE) uptake inhibitors desipramine (DMI) or (+)-oxaprotiline or the inactive (-)-enantiomer of oxaprotiline. DMI, as previously reported, significantly increased hippocampal glucocorticoid receptor (GR) mRNA while the equipotent NE uptake inhibitor (+)-oxaprotiline like the inactive (-)-oxaprotiline did not alter hippocampal levels of GR mRNA. The results indicate that an increase in the synaptic availability of NE as a consequence of uptake inhibition is not responsible for the action of DMI on GR gene expression.

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“…Repeated doses of (+)-OXA, but not ( -)-OXA. reduce the density of J3-adrenoceptors in the rat brain cortex (Mishra et al, 1982;Delini-Stula et al, 1983) and desensitise the NA-sensitive adenylate cyclase (Mishra et al, 1982;Kopanski et al, 1983). Our recent experin-tems demonstrated that both these enantiomers, administered repeatedly but not in the single dose, increase locomotor hyperactivity induced by dopamine agonists (Maj and W~dzony, 1988).…”

Section: J Maj Et Almentioning

confidence: 96%

Some central pharmacological effects of (+)- and (−)-oxaprotiline

Rogóż

Skuza

et al. 1990

J. Neural Transmission

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The central action of oxaprotiline (OXA) enantiomers, administered in a single dose, was studied in rats and mice. (+)-OXA and (-)-OXA attenuated reserpine- and apomorphine-induced hypothermia [(+)-OXA in a more potent manner] in mice and reduced the immobility time in the behavioural despair test in rats. Both OXA enantiomers inhibited locomotor activity in mice and rats, and enhanced and prolonged amphetamine- and apomorphine-induced stereotypy in rats. (-)-OXA potentiated the amphetamine hyperactivity in rats, but not in mice. Nomifensine hyperactivity in rats was unaffected by either enantiomer, and locomotor hypoactivity induced by low doses of apomorphine was also unchanged, as was L-DOPA-induced locomotor hyperactivity in mice. Apomorphine-induced climbing in mice was attenuated by (+)-OXA. Clonidine locomotor hypoactivity and hypothermia were unchanged, and clonidine-induced aggressiveness was attenuated by (+)-OXA. Neither OXA enantiomer affected the action of oxotremorine. In some tests the effect of OXA was stronger at 3 h than at 1 h after administration. The above results indicate that both OXA enantiomers--in particular (-)-OXA--increase some dopaminergic behavioural effects in rats.

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Oxaprotiline: Induction of central noradrenergic subsensitivity by its (+)-enantiomer

Cited by 32 publications

References 12 publications

The acute and chronic effects of (+) and (−) oxaprotiline upon melatonin secretion in normal subjects

The acute and chronic effects of (+) and (−) oxaprotiline upon melatonin secretion in normal subjects

Increased synaptic availability of norepinephrine following desipramine is not essential for increases in GR mRNA

Some central pharmacological effects of (+)- and (−)-oxaprotiline

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