The mechanism of action of alpha 2 adrenoceptor blockers as revealed by effects on open field locomotion and escape reactions in the shuttle-box.
The precise mechanism of action of alpha 2 adrenoceptor blockers in 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 alpha 2 adrenoceptors. We postulate that if the presynaptic actions of the antagonists prevail, the enhanced norepinephrine release leads to an activation of postsynaptic alpha 1 or beta adrenoceptors. In this case the effects of alpha 2 adrenoceptor blockers can be reversed by antagonists acting on the latter two adrenoceptors, since postsynaptic alpha 2 adrenoceptors are also blocked. If the postsynaptic blockade of alpha 2 adrenoceptors is the main cause of effects, than the blockade of alpha 1 or beta adrenoceptors should not reverse the action of alpha 2 blockers. The alpha 2 blocker idazoxan (dose 0.5-5 mg/kg) increased locomotor activity in an open field, an effect that was abolished by both alpha 1 and beta 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 alpha 1 or beta receptor blockade. These results suggest that the mechanism of action of alpha 2 adrenoceptor blockers depends on which effects are studied. Exploration seems to be affected by a presynaptic mechanism as neurons bearing postsynaptic alpha 1 or beta adrenoceptors are involved in the control of this behavior, while escape reactions appear to be affected by the postsynaptic blockade of alpha 2 adrenoceptors (i.e. neurons bearing postsynaptic alpha 2 adrenoceptors are involved in its control). Thus, there is no generalized mechanism of action for alpha 2 adrenoceptor blockers; their precise mode of action should be investigated in each particular case.
Haller
J
J
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Makara
G B
GB
Pintér
I
I
Gyertyán
I
I
Egyed
A
A
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects*; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan