The pharmacology of sibutramine hydrochloride (BTS 54 524), a new antidepressant which induces rapid noradrenergic down-regulation

@article{Buckett1988ThePO,
  title={The pharmacology of sibutramine hydrochloride (BTS 54 524), a new antidepressant which induces rapid noradrenergic down-regulation},
  author={W. Roger Buckett and P. C. Thomas and Graham P. Luscombe},
  journal={Progress in Neuro-Psychopharmacology and Biological Psychiatry},
  year={1988},
  volume={12},
  pages={575-584}
}
1. Sibutramine hydrochloride (BTS 54 524) has been evaluated in a range of behavioural and biochemical models predictive of potential antidepressant activity. 2. BTS 54 524 exhibited potent activity in acute behavioural tests for detecting potential antidepressants. 3. BTS 54 524 rapidly and potently down-regulated rat cortical beta-adrenoceptors, being effective after only three days of oral administration. 4. BTS 54 524 showed very little activity in a range of experiments predictive of side… 
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Antidepressant treatments, including electroconvulsive shock and the putative antidepressant sibutramine hydrochloride, do not alter [3H]-prazosin binding to rat cortical membranes
TLDR
Treatment for 1, 3 or 10 days with sibutramine hydrochloride, desi pramine, amitriptyline, or pargyline did not effect the number or affinity of α1-adrenoceptors as determined by [3H]-prazosin binding to rat cerebral cortical membranes.
The contribution of metabolites to the rapid and potent down-regulation of rat cortical β-adrenoceptors by the putative antidepressant sibutramine hydrochloride
TLDR
The potent inhibition of the reuptake of noradrenaline by the secondary and primary amine metabolites probably contributes to the rapid and potent down-regulation of beta-adrenoceptors in the rat, induced by the putative antidepressant sibutramine HCl.
Effects of sibutramine on anxiety-related behaviours in rats.
TLDR
In contrast to what has been reported with drugs such as the tricyclic anti-depressants that also inhibit monoamine reuptake, the anxiolytic effects of sibutramine were revealed after a single administration.
Absence of sibutramine effect on spontaneous anxiety in rats.
TLDR
The acute and chronic administration of sibutramine is not related to anxiolytic or anxiogenic effects, and the maximum effect of anti-obesity in rats, did not interfere with anxiety.
A comparison of the effects of sibutramine hydrochloride, bupropion and methamphetamine on dopaminergic function: evidence that dopamine is not a pharmacological target for sibutramine
TLDR
The data indicate that dopamine is unlikely to be an important pharmacological target for reuptake inhibition by sibutramine, and the rank order of potency for enhancing central dopaminergic function is methamphetamine > bupropion >> sibUTramine.
A comparison of various antidepressant drugs demonstrates rapid desensitisation of α2-adrenoceptors exclusively by sibutramine hydrochloride
TLDR
This comparative study using antidepressant treatments with differing pharmacological modes of action demonstrated that sibutramine was the only drug which rapidly down-regulated pre- and postsynaptic α2-adrenoceptors.
Sibutramine. A review of its contribution to the management of obesity.
TLDR
Obese patients with type 2 (non-insulin-dependent) diabetes or hypertension lost significantly more mean bodyweight with sibutramine than with placebo, although weight loss was less than that in obese patients without comorbidities, and concerns over potential pressor effects are reflected in the manufacturer's dosage and administration recommendations.
Thermogenic effects of sibutramine and its metabolites
The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO2) in rats treated with…
Abuse liability assessment of sibutramine, a novel weight control agent
TLDR
Data indicate sibutramine lacks amphetamine-type abuse liability when administered acutely, and is likely to have low abuse potential when administered in the therapeutic range.
Sibutramine: a novel new agent for obesity treatment.
TLDR
Sibutramine, 5 and 20 mg/day, produced a dose-related weight loss in obese subjects compared to placebo in an 8-week trial and shows promise as an antiobesity drug.
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