caa a22 4500 469120843 CHVBK 20180323133138.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF02245262 doi (NATIONALLICENCE)springer-10.1007/BF02245262 A comparison of various antidepressant drugs demonstrates rapid desensitisation of α2-adrenoceptors exclusively by sibutramine hydrochloride [Elektronische Daten] [David Heal, Michael Prow, Jane Gosden, Graham Luscombe, W. Buckett] The functional status of presynaptic and post-synaptic α2-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 α2-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 α2-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 α2-adrenoceptors. ECS down-regulated postsynaptic α2-adrenoceptors when given for 3 days, but required 5 days to desensitise both α2-adrenoceptor populations. Springer-Verlag, 1992 α2-Adrenoceptors nationallicence Presynaptic α2-adrenoceptors nationallicence Postsynaptic α2-adrenoceptors nationallicence Clonidine-induced behaviours nationallicence Sedation nationallicence Hypoactivity nationallicence Mydriasis nationallicence Sibutramine hydrochloride nationallicence Electroconvulsive shock nationallicence Antidepressants nationallicence Heal David Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut Prow Michael Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut Gosden Jane Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut Luscombe Graham Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut Buckett W. Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut Psychopharmacology Springer-Verlag 107/4(1992-06-01), 497-502 0033-3158 107:4<497 1992 107 213 https://doi.org/10.1007/BF02245262 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245262 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Heal David Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 700 1- Prow Michael Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 700 1- Gosden Jane Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 700 1- Luscombe Graham Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 700 1- Buckett W. Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 107/4(1992-06-01), 497-502 0033-3158 107:4<497 1992 107 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer