Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers.

King, DJ; Devaney, N.

doi:10.1111/j.1365-2125.1988.tb05303.x

Cited by 43 publications

(20 citation statements)

References 10 publications

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“…33 Our results show, however, that 10 mg and 15 mg sibutramine treatments were associated with a signi®cant increase in heart rate, compared with the placebo. Such observations have previously been reported by King and Devaney 13 in healthy volunteers with a single dose of 45 mg or 60 mg sibutramine. Cole et al 14 also reported changes in heart rate following once-daily doses of 20 mg or 30 mg sibutramine.…”

Section: Discussionsupporting

confidence: 70%

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Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study

Hanotin

Thomas

Jones³

et al. 1997

Int J Obes

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OBJECTIVES: To assess the weight-reducing effects and tolerability of 5 mg, 10 mg and 15 mg daily doses of sibutramine, a novel serotonin and noradrenaline reuptake inhibitor (SNRI). DESIGN: Multicentre, double-blind, and placebo-controlled study. After a one week run-in period, patients were randomized to receive placebo or sibutramine over a 12-week period. Advice on diet and behaviour modi®cation was provided. One follow-up was conducted four weeks after cessation of treatment. SUBJECTS: 235 obese outpatients, aged 18±65 y with a body mass index (BMI) within the range 27±40 kgam 2 . MEASUREMENTS: Weight, height, waist and hip circumference, and medical history, assessment of hunger, satiety, appetite and craving for sweet, savoury and carbohydrate foods, and also for carbohydrate snacking, standard laboratory assessments, blood pressure, heart rate and ECG. RESULTS: The group mean ( AE s.e.m.) weight loss at end-point was 1.4 AE 0.5 kg for placebo (n 59), 2.4 AE 0.5 kg for 5 mg sibutramine (n 56), 5.1 AE 0.5 kg for 10 mg sibutramine (n 59) and 4.9 AE 0.5 kg (n 62) for 15 mg sibutramine. The difference observed between the placebo and the 10 mg and 15 mg groups was statistically signi®cant from week 2 onwards (P`0.01), but there was no signi®cant difference between these sibutramine groups. The percentage of patients losing b 5% of initial bodyweight was signi®cantly greater for 15 mg sibutramine (55%) and 10 mg sibutramine (49%) than for treatment with placebo (19%), (P`0.001). During the double-blind period, 41 patients (17%) withdrew prematurely and 168 patients (71%) reported 453 adverse events. The incidence and type of adverse event and the rates of withdrawal, were not signi®cantly different in the four groups. No signi®cant differences between the groups were observed, in respect of changes in systolic and diastolic blood pressure, but a signi®cant increase in heart rate (about 4 beatsamin) was noted for patients who received 10 mg or 15 mg sibutramine, compared with the placebo (P`0.001).CONCLUSION: These data demonstrate dose-related weight loss with sibutramine treatment for up to 12 weeks in obese patients. Doses of 10 mg and 15 mg once daily were shown to be similarly effective, well tolerated and signi®cantly more effective than the placebo.

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Section: Discussionsupporting

confidence: 70%

“…9±12 In healthy volunteers, sibutramine appears to be free from anticholinergic effects. 13 It has no amphetamine-like abuse potential in either animals 8 or recreational drug users. 14 In rats, sibutramine causes a dose-dependent decrease in food intake and bodyweight.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study

Hanotin

Thomas

Jones³

et al. 1997

Int J Obes

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“…In human, the acute administration of a single dose of sibutramine elevated systolic blood pressure and heart rate (HR) for at least 6 h (King and Devaney, 1988). Furthermore, chronic treatment of obese patients with sibutramine (20 mg day Ϫ1 for 6 months), caused modest, but significant, increases in mean arterial blood pressure (MAP) (2-3 mm Hg) and HR (3)(4)(5) beats min Ϫ1 ) (Fujioka et al, 2000).…”

mentioning

confidence: 99%

Acute Cardiovascular Effects of Sibutramine in Conscious Rats

Woolard

Bennett²,

Dunn³

et al. 2003

J Pharmacol Exp Ther

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Sibutramine is a serotonin and norepinephrine reuptake inhibitor, used in the treatment of obesity. In this study, cardiovascular effects of sibutramine (0.9, 3, or 9 mg kg Ϫ1 i.p.) were measured in conscious Sprague-Dawley rats, in the absence and presence of ␤-and/or ␣-adrenoceptor antagonism (with propranolol and/or phentolamine, respectively). Sibutramine caused pressor and tachycardic effects, with celiac and mesenteric vasoconstrictions, and hyperemic hindquarters vasodilatation. Pretreatment with propranolol inhibited the tachycardic and hindquarters vasodilator effect of sibutramine, whereas phentolamine inhibited the pressor and vasoconstrictor effects of sibutramine. In the presence of phentolamine, sibutramine caused hyperemic mese nteric vasodilatation. In preconstricted, isolated, mesenteric vessels, sibutramine and its metabolites BTS 54 505 (N-desmethylsibutramine) and BTS 54 354 (N-didesmethylsibutramine) (10 M) produced significant vasodilatations. Neither sibutramine nor BTS 54 505 enhanced vessel sensitivity to norepinephrine, whereas BTS 54 354 produced a significant leftward shift in the concentration-response curve to norepinephrine. Collectively, the results indicate that the overt cardiovascular effects of sibutramine involve ␣-adrenoceptor-mediated celiac and mesenteric vasoconstrictions, and ␤-adrenoceptor-mediated hindquarters vasodilatation and tachycardia. The mesenteric vasodilator response to sibutramine, seen in the presence of phentolamine, may be a direct effect of the drug and/or its metabolites, on vessel tone. The cardiovascular effects of sibutramine in vivo may be secondary to inhibition of peripheral and/or central reuptake of monoamines by the metabolites BTS 54 354 and/or BTS 54 505. It remains to explain why BTS 54 354, but not BTS 54 505, enhanced norepinephrine sensitivity in vitro, because both metabolites are potent inhibitors of the norepinephrine transporter.

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“…No entanto, estudos clínicos não evidenciaram eficácia antidepressiva. [15][16][17] De forma diferente, não existe evidência de redução dos sintomas relacionados ao TOC com o uso dessas substâncias.…”

Section: Russelunclassified

Transtorno da compulsão alimentar periódica e transtorno obsessivo-compulsivo: partes de um mesmo espectro?

Papelbaum¹,

Appolinário²

2001

Rev. Bras. Psiquiatr.

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Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers.

Cited by 43 publications

References 10 publications

Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study

Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study

Acute Cardiovascular Effects of Sibutramine in Conscious Rats

Transtorno da compulsão alimentar periódica e transtorno obsessivo-compulsivo: partes de um mesmo espectro?

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