Uses
A metabolite of Sibutramine, a serotonin and noradrenaline reuptake inhibitor (SNR). Decreases calorie intake and increases energy expenditure.
Uses
A metabolite of Sibutramine, a serotonin and noradrenaline reuptake inhibitor (SNR). Decreases calorie intake and increases energy expenditure.
Biological Activity
Potently active primary amine metabolite of sibutramine (1-(4-Chlorophenyl)-N,N-dimethyl-a-(2-methylpropyl)cyclobutanemethanamine hydrochloride ) that exhibits a similar pharmacological profile to the parent compound. Inhibits serotonin and noradrenalin reuptake more potently than sibutramine in vitro . In vivo, reduces food intake in rodents following i.c.v. administration and increases energy expenditure via thermogenesis.
in vitro
simultaneous application of bts 54-505 with 5-ht resulted in a prolongation of the recovery time from the 5-ht-mediated suppression of discharge activity. bts 54-505 also prolonged the recovery time from a na-mediated potentiation of firing. these effects on recovery time are attributed to the inhibition of uptake of both 5-ht and na by bts 54-505. the amplitude of the response to 5-ht or na was unaffected by co-ejection of bts 54-505 [1].
in vivo
the secondary (bts 54-354) and primary (bts 54-505) amine metabolites of sibutramine hcl exhibit similar in vivo pharmacological activity to the parent compound. thus, each compound displays potent activity in acute behavioural models predictive of antidepressant effects and a comparable ability to inhibit the uptake of monoamines [2].
IC 50
0.066 μm for noradrenaline uptake; 5.1 μm for 5-ht uptake; 0.31 μm for dopamine uptake
References
[1] scott g, luscombe gp, mason r. the effects of bts 54-505, a metabolite of sibutramine, on monoamine and excitatory amino acid-evoked responses in the rat dorsolateral geniculate nucleus in vivo. br j pharmacol. 1994 jan;111(1):97-102.
[2] luscombe gp, hopcroft rh, thomas pc, buckett wr. the contribution of metabolites to the rapid and potent down-regulation of rat cortical beta-adrenoceptors by the putative antidepressant sibutramine hydrochloride. neuropharmacology. 1989 feb;28(2):129-34.
