The precise mechanism of action of α2 adrenoceptor blockers is not known, although in principle they have two main effects: (i) they stimulate the norepinephrinergic system by inhibiting the negative feed back of norepinephrine release (presynaptic effect) and (ii) they inhibit the effects of norepinephrine on postsynaptic α2 adrenoceptors. We postulate that if the presynaptic actions of the antagonists prevail, the enhanced norepinephrine release leads to an activation of postsynaptic α1 or β adrenoceptors. In this case the effects of α2 adrenoceptor blockers can be reversed by antagonists acting on the latter two adrenoceptors, since postsynaptic α2 adrenoceptors are also blocked. If the postsynaptic blockade of α2 adrenoceptors is the main cause of effects, than the blockade of α1 or β adrenoceptors should not reverse the action of α2 blockers. The α2 blocker idazoxan (dose 0.5-5 mg/kg) increased locomotor activity in an open field, an effect that was abolished by both α1 and β receptor blockers (prazosin and propranolol, respectively). Escape responses in a shuttle box were strongly suppressed by idazoxan (0.5-2 mg/kg). However, this effect was not changed by concomitant α1 or β receptor blockade. These results suggest that the mechanism of action of α2 adrenoceptor blockers depends on which effects are studied. Exploration seems to be affected by a presynaptic mechanism as neurons bearing postsynaptic α1 or β adrenoceptors are involved in the control of this behavior, while escape reactions appear to be affected by the postsynaptic blockade of α2 adrenoceptors (i.e. neurons bearing postsynaptic α2 adrenoceptors are involved in its control). Thus, there is no generalized mechanism of action for α2 adrenoceptor blockers; their precise mode of action should be investigated in each particular case.
- Open field
ASJC Scopus subject areas