Biological Activity
arc 239 dihydrochloride is a selective antagonist of α2b adrenoceptor with pkd value of 8.8 [1].α2b adrenoceptor is a g-protein coupled receptor. α2-adrenergic receptors include three subtypes: α2a, α2b and α2c, which play an important role in regulating neurotransmitter release from adrenergic neurons in the central nervous system and from sympathetic nerves.arc 239 dihydrochloride is a selective α2b adrenoceptor antagonist. in rat brain, arc 239 inhibited the binding of 5-htia receptor radioligands 8-oh-dpat and rx 821002 to cortical membranes with ki values of 63.1 and 136 nm respectively, which suggested that arc 239 recognized 5-ht1a receptor [2]. treatment human platelets with arc 239 significantly inhibited platelet aggregation induced by adenosine diphosphate (adp), epinephrine and arachidonic acid and increased collagen/epinephrine closure time, which suggested that α2b adrenoceptor play a critical role in platelet aggregation [3]. in cervical samples isolated from pregnant rats, arc 239 effectively inhibited noradrenaline-stimulated contractions [4].in c57bl/6 mice with gastric mucosal damage induced by acidified ethanol, arc 239 (10.4 nm) antagonized gastroprotective effect induced by α2-adrenoceptor agonists [5].
References
[1]. bylund db, ray-prenger c, murphy tj. alpha-2a and alpha-2b adrenergic receptor subtypes: antagonist binding in tissues and cell lines containing only one subtype. j pharmacol exp ther, 1988, 245(2): 600-607.
[2]. meana jj, callado lf, pazos a, et al. the subtype-selective alpha 2-adrenoceptor antagonists brl 44408 and arc 239 also recognize 5-ht1a receptors in the rat brain. eur j pharmacol, 1996, 312(3): 385-388.
[3]. marketou me, kintsurashvili e, androulakis ne, et al. blockade of platelet alpha2b-adrenergic receptors: a novel antiaggregant mechanism. int j cardiol, 2013, 168(3): 2561-2566.
[4]. gál a, kolarovszki-sipiczki z, et al. the effect of the arc 239 on the myometrial and cervical action in the rat, in vitro. acta pharm hung, 2009, 79(2): 75-80.
[5]. zádori zs, shujaa n, brancati sb, et al. both α2b- and α2c-adrenoceptor subtypes are involved in the mediation of centrally induced gastroprotection in mice. eur j pharmacol, 2011, 669(1-3): 115-120.
