A comparison of various antidepressant drugs demonstrates rapid desensitisation of alpha 2-adrenoceptors exclusively by sibutramine hydrochloride
by
Heal DJ, Prow MR, Gosden J, Luscombe GP, Buckett WR
Boots Pharmaceuticals Research Department, Nottingham, UK.
Psychopharmacology (Berl) 1992; 107(4):497-502

ABSTRACT

The functional status of presynaptic and postsynaptic alpha 2-adrenoceptors in murine brain was respectively monitored using the hypoactivity (sedation) and mydriasis (pupil dilatation) responses to clonidine (0.1 mg/kg IP). Both responses were attenuated 24 h after 3 days of injection of sibutramine hydrochloride (3 mg/kg IP). To ascertain whether this property was exclusive to sibutramine, the following antidepressant drugs were also tested for their ability to down-regulate alpha 2-adrenoceptors rapidly: amitriptyline, doxepin, nomifensine, desipramine, amoxapine, fluoxetine, zimeldine, tranylcypromine and mianserin. When given for 3 or 5 days at the low dose of 3 mg/kg IP, none of the other antidepressants reduced clonidine-induced hypoactivity or mydriasis. Furthermore, increasing the dose of amitriptyline, doxepin, nomifensine, desipramine, amoxapine and tranylcypromine to 10 mg/kg IP did not enable these antidepressants to attenuate the alpha 2-adrenoceptor-mediated responses after 3 days of treatment. An electroconvulsive shock (ECS; 200 V, 2 s) given once daily attenuated clonidine-induced mydriasis, but not hypoactivity, when administered for 3 days and both responses when administered for 5 days. In conclusion, 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 alpha 2-adrenoceptors. ECS down-regulated postsynaptic alpha 2-adrenoceptors when given for 3 days, but required 5 days to desensitise both alpha 2-adrenoceptor populations.

Doxepin
Mianserin
Fluoxetine
Amoxapine
Sibutramine
Nomifensine
Desipramine
Amphetamines
Tranylcyromine
Sibutramine abuse
New slimming drugs
Beta-adrenoeceptors
Sibutramine compared
Sibutramine and obesity
Alpha-2 adrenoreceptors
Sibutramine v dexfenfluramine
Sibutramine as an antidepressant
Sibutramine: clinical pharmacology
Sibutramine, noradrenaline and serotonin

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family