Summary
A series of 8 clonidine-like substances were tested in rats on central sympathoinhibition (heart rate decrease in vagotomized rats, D50=dose which decreased heart rate by 50 beats/min), peripheral postsynaptic activity (blood pressure increase in spinal rast, PD 30=dose which increased blood pressure 30 mm Hg) and peripheral presynaptic activity (inhibition of tachycardia as elicited by electrical stimulation in the spinal canal of pithed rats, ID 50=dose which inhibited for 50%). The D50, PD30 and ID50 were converted in moles/kg and the negative logarithms thereof were correlated. There was a good correlation between the central effect (D50) and both peripheral effects (PD30 and ID50, respectively; r=0.89 and 0.91, respectively) provided one drug with low lipoid affinity was omitted from calculation (St 600). There was also good correlation between both peripheral effects (PD30 and ID50; r=0.94) and this could be extended to other imidazolines which are not acting centrally as antihypertensives (oxymetazoline, naphazoline, St 91, tramazoline; r=0.90). The results were interpreted by (1) the agonistic activity of the clonidinelike drugs mainly at α2-adrenoceptors and (2) the presence of α2-adrenoceptors at peripheral presynaptic, peripheral postsynaptic as well as central cardiovascular sites.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andén NE, Grabowska M, Strömbom U (1976) Different alphaadrenoceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedeberg's Arch Pharmacol 292:43–52
Berthelsen S, Pettinger WA (1977) A functional basis for classification of α-adrenergic receptors. Life Sci 21:595–606
Borowski E, Starke K, Ehrl H, Endo T (1977) A comparison of pre- and postsynaptic effects of α-adrenolytic drugs in the pulmonary artery of the rabbit. Neuroscience 2:285–296
Drew MG (1976) Effects of α-adrenoceptor agonists and antagonists on pre- and postsynaptically located α-adrenoceptors. Eur J Pharmacol 36:313–320
Haeusler G (1974) Clonidine-induced inhibition of sympathetic nerve activity: No indication for a central presynaptic or an indirect sympathomimetic mode of action. Naunyn-Schmiedeberg's Arch Pharmacol 286:97–111
Hammer R, Kobinger W, Pichler L (1980) Binding of an imidazolidine (clonidine), an oxazoloazepin (B-HT 933) and a thiazoloazepin (B-HT 920) to rat brain α-adrenoceptors and relation to cardiovascular effects. Eur J Pharmacol 62:277–285
Hoefke W, Kobinger W, Walland A (1975) Relationship between activity and structure in derivatives of clonidine. Arzneim Forsch 25:786–793
Kobinger W (1978) Central α-adrenergic systems as targets for hypotensive drugs. Rev Physiol Biochem Pharmacol 81:39–100
Kobinger W, Pichler L (1974) Evidence for direct α-adrenoceptor stimulation of effector neurons in cardiovascular centers by clonidine. Eur J Pharmacol 27:151–154
Kobinger W, Pichler L (1975a) The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline. Eur J Pharmacol 30:56–62
Kobinger W, Pichler L (1975b) Investigation into some imidazoline compounds, with respect to peripheral α-adrenoceptor stimulation and depression of cardiovascular centers. Naunyn-Schmiedeberg's Arch Pharmacol 291:175–191
Kobinger W, Pichler L (1976) Centrally induced reduction in sympathetic tone — a postsynaptic α-adrenoceptor-stimulating action of imidazolines. Eur J Pharmacol 40:311–320
Kobinger W, Pichler L (1977) Pharmacological characterization of B-HT 933 [2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-(5,4-d)-azepin-dihydrochloride] as a hypotensive agent of the “clonidine-type”. Naunyn-Schmiedeberg's Arch Pharmacol 300:39–46
Kobinger W, Pichler L (1980) Investigation into different types of post- and presynaptic α-adrenoceptors at cardiovascular sites in rats. Eur J Pharmacol 65:393–402
Kobinger W, Walland A (1973) Modulating effect of central adrenergic neurones on a vagally mediated cardioinhibitory reflex. Eur J Pharmacol 22:344–350
Langer SZ (1977) Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol 60:481–497
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
Pichler L, Placheta P, Kobinger W (1980) Effect of azepexole (B-HT 933) on pre- and postsynaptic α-adrenoceptors at peripheral and central nervous sites. Eur J Pharmacol 65:233–241
Pittner H, Stormann H, Enzenhofer R (1976) Pharmacodynamic actions of midodrine, a new α-adrenergic stimulating agent, and its main metabolite, ST 1059, Arzneim Forsch 26:2145–2154
Robson RD, Antonaccio MJ, Saelens JK, Liebman J (1978) Antagonism by mianserin and classical α-adrenoceptor blocking drugs of some cardiovascular and behavioral effects of clonidine. Eur J Pharmacol 47:431–442
Sachs L (1972) Statistische Auswertmethoden. 3. Aufl.: Springer, Berlin Heidelberg New York
Schmitt H (1977) The pharmacology of clonidine and related products. In: Gross F (ed) Handbuch der experimentellen Pharmakologie, vol 39. Springer, Berlin Heidelberg New York, p 299
Schmitt H, Schmitt H, Fénard S (1973) Action of α-adrenergic blocking drugs on the sympathetic centres and their interaction with the central sympatho-inhibitory effect of clonidine. Arzneim Forsch 23:40–45
Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–124
Starke K, Langer SZ (1979) A note on terminology for presynaptic receptors. In: Langer SZ, Starke K, Dubocovich ML (eds) Presynaptic receptors, advances in biosciences, vol 18. Pergamon Press, Oxford London, p 1
Starke K, Borowski E, Endo T (1975a) Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur J Pharmacol 34:385–388
Starke K, Endo T, Taube HD (1975b) Relative pre- and postsynaptic potencies of α-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 291:55–78
Tanaka T, Starke K (1979) Binding of 3H-clonidine to an α-adrenoceptor in membranes of guinea pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 309:207–215
Timmermans PBMWM (1980) A simple method for the discrimination between α1- and α2-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 311:R59
Timmermans PBMWM, Van Zwieten PA (1977) Central and peripheral α-adrenergic effects of some imidazolidines. Eur J Pharmacol 45:229–236
Timmermans PBMWM, Brands A, Van Zwieten PA (1977) Lipophilicity and brain disposition of clonidine and structurally related imidazolines. Naunyn-Schmiedeberg's Arch Pharmacol 300:217–226
Wikberg JES (1979) The pharmacological classification of adrenergic α1 and α2 receptors and their mechanisms of action. Acta Physiol Scand (Suppl) 468:1–99
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kobinger, W., Pichler, L. Relation between central sympathoinhibitory and peripheral pre-and postsynaptic α-adrenoceptors as evaluated by different clonidine-like substances in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 315, 21–27 (1980). https://doi.org/10.1007/BF00504226
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00504226