Summary
-
1.
RX781094 [2-(2-(1,4-benzodioxanyl))-2-imidazoline HCl] is a new α2 adrenoceptor selective antagonist. Its effects on cardiovascular response “in vivo” before and after administration of α1 and α2 adrenoceptor agonists have been studied in conscious and anaesthetized rabbits. The affinity of RX781094 for α1 and α1 adrenoceptors has been investigated “in vitro” in radioligand binding studies.
-
2.
Intravenous injection of RX781094 caused an immediate short lived pressor response which was attenuated by α1 and α2 adrenoceptor antagonists; it also caused a prolonged bradycardia.
-
3.
Pretreatment with intravenous RX 781094 inhibited the hypotensive response to both intravenous and intracisternal clonidine in a dose dependent manner.
-
4.
RX781094 also showed a dose dependent inhibition of the acute pressor response to the α2 adrenoceptor selective agonist guanabenz.
-
5.
Pressor dose response curves to noradrenaline, a mixed α1/α2 adrenoceptor agonist were shifted to the right after RX781094 whereas those to the α1 adrenoceptor agonist phenylephrine were unchanged.
-
6.
RX781094 was more effective at displacing specifically bound 3H clonidine than 3H prazosin in membrane preparations from rabbit brain.
-
7.
These observations are consistent with a selective α2 adrenoceptor antagonist effect of RX781094 at central and peripheral adrenoceptors in the rabbit.
Similar content being viewed by others
References
Berridge TL, Doxey JC, Roach AG (1982) Antagonism of clonidine induced hypotension and bradycardia by RX781094 and other α adrenoceptor antagonists in the rat. Br J Pharmacol 75:139P
Berthelot A, Hamilton CA, Petty MA, Reid JL (1982) Central and peripheral α adrenoceptor number and responsiveness after sino-aortic denervation in the rabbit. J Cardiovasc Pharmacol 4:567–574
Berthelsen S, Pettinger WH (1977) A functional basis for classification of α adrenergic receptors. Life Sci 21:595–606
Cambridge D, Davey MJ, Massingham R (1977) The pharmacology of antihypertensive drugs with special reference to vasodilators, α adrenergic blocking drugs and prazosin. Med J Aust (2 suppl) 1:2–6
Chalmers J, Wurtman RJ (1971) Participation of central noradrenergic neurons in arterial baroreceptor reflexes in the rabbit. Circ Res 23:480–491
Chalmers J, Reid JL (1972) Participation of central noradrenergic neurons in arterial baroreceptor reflexes in the rabbit: A study with intracisternally administered 6-hydroxydopamine. Circ Res 31:789–804
Chapleo CB, Doxey JL, Myers PL, Roach AG (1981) RX781094, a new potent selective antagonist of α2 adrenoceptors. Br J Pharmacol 74:842 P
Dabiré H, Mouille P, Andréjak M, Fournier B, Schmitt H (1981) Pre- and post-synaptic α adrenoceptor blockade by (imidazolinyl-2)-2-Benzodioxane 1–4 (170 150): Antagonistic action on central effects of clonidine. Arch Int Pharmacodyn 254:262–270
Dettmar PW, Lynn AG, Tulloch IF (1981) Neuropharmacological evaluation of RX781094 a new selective α2 adrenoceptor antagonist. Br J Pharmacol 74:843 P
Docherty JR, McGrath JC (1980) A comparison of pre- and post-junctional potencies of several alpha-adrenoceptor agonists in the cardiovascular system and anococcygeus muscle of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 312:107–116
Dollery CT, Reid JL (1973) Central noradrenergic hormones and the cardiovascular actions of clonidine in the rabbit. Br J Pharmacol 47:206–216
Doxey JC, Smith CFC, Walker JM (1977) Selectivity of blocking agents for pre and post synaptic α adrenoceptors. Br J Pharmacol 60:91–96
Drew GM (1977) Effects of α adrenoceptor agonists and antagonists on pre and postsynaptically located adrenoceptors. Eur J Pharmacol 60:91–96
Drew GM, Whiting SB (1979) Evidence for two distinct types of postsynaptic adrenoceptor in vascular smooth muscle in vivo. Br J Pharmacol 67:207–215
Elliott HL, McLean K, Summer DJ, Reid JL (1981) Pharmacodynamic studies on mianserin and its interaction with clonidine. Eur J Clin Pharmacol 21:97–102
Grant JA, Scrutton MC (1979) Novel 227-3 adrenoceptors primarily responsible for inducing human platelet aggregation. Nature (Lond) 277:659–661
Haeusler G (1976) Studies on the possible contribution of a peripheral presynaptic action of clonidine and dopamine to their vascular effects under in vivo conditions. Naunyn-Schmiedeberg's Arch Pharmacol 295:191–202
Hamilton CA, Reid JL (1981) Changes in α adrenoceptors during long term treatment of rabbits with prazosin. J Cardiovasc Pharmacol 3:977–985
Hamilton CA, Reid JL (1982) A postsynaptic location of 227-4 adrenoceptors in vascular smooth muscle: in vivo studies in the conscious rabbit. Cardiovasc Res 16:11–15
Hamilton CA, Reid JL, Zamboulis C (1982b) The role of presynaptic α adrenoceptors in the regulation of blood pressure in the conscious rabbit. Br J Pharmacol 75:417–424
Karliner B, Barnes P, Hamilton CA, Dollery CT (1979) Alpha1 adrenergic receptors in guinea pig myocardium: Identification by binding of a new radioligand [3H]prazosin. Biochem Biophys Res Commun 16:375–384
Kobinger W (1978) Central α adrenergic systems as targets for hypotensive drugs. Rev Physiol Biochem Pharmacol 81:31–39
Langer SZ (1974) Presynaptic regulation of catecholamine release. Biochem Pharmacol 23:1793–1800
Langer SZ (1977) Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol 60:481–498
Mouille P, Dabiré H, Fournier B, Schmitt H (1981) A further attempt to characterise the 227-5 adrenoceptor blocking properties of (imidazolyl-2)-2-benzodioxane 1–4 (170 150) in pithed rats. Eur J Pharmacol 73:367–370
Pichler L, Kobinger W (1978) Presynaptic activity at peripheral adrenergic sites and blood pressure effect of α adrenoceptor stimulating drugs. Eur J Pharmacol 52:287–295
Reid JL, Hamilton CA (1980) Catecholamines and blood pressure regulation: The role of α-adrenoceptors. J Cardiovasc Res 2(53):325–330
Reid JL, Tangri KK, Wing CMH (1977) The central hypotensive action of clonidine and propranolol in animals and man. Prog Brain Res 47:369–384
Schmitt H, Mme Schmitt M, Boissier JR, Guidicelli JF (1967) Centrally mediated decrease in sympathetic tone induced by 2-(2,6-dichlorophenylamino)-2-imidazoline (ST 155), catapresan) Eur J Pharmacol 2:147–148
Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–24
Starke K, Docherty JR (1980) Recent developments in alpha adrenoceptor research. J Cardiovasc Pharmacol Suppl (2) 3:269–286
Starke K, Langer SZ (1979) A note on terminology for presynaptic receptors. In: Langer SZ, Starke K, Dubocovich ML (eds) Advances in the biosciences, Presynaptic receptors, vol 18, Pergamon Press, Oxford, pp 1–3
Tanaka T, Weitzell R, Starke K (1978) High selectivity of rauwolscine for presynaptic α adrenoceptors. Eur J Pharmacol 52:239–240
Timmermans PBMWM, Kwa HY, van Zwieten PA (1979) Possible subdivision of postsynaptic α adrenoceptors mediating pressor responses in the pithed rat. Naunyn Schmiedeberg's Arch Pharmacol 310:189–193
Timmermans PBMWM, Schoop AMC, Kwa HY, van Zwieten PA (1981) Characterisation of α adrenoceptors participating in the central hypotensive and sedative effects of clonidine using yohimbine, rauwolscine and corynanthine. Eur J Pharmacol 70:7–15
Weitzell R, Tanaka T, Starke K (1979) Pre and post synaptic effects of yohimbine steroisomers on noradrenergic transmission in the pulmonary artery of the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 303:127–136
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hannah, J.A.M., Hamilton, C.A. & Reid, J.L. RX781094, a new potent α2 adrenoceptor antagonist. Naunyn-Schmiedeberg's Arch. Pharmacol. 322, 221–227 (1983). https://doi.org/10.1007/BF00500769
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00500769