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RILMENIDINE ACTS AS A PARTIAL AGONIST AT PREJUNCTIONAL α 2 ‐ADRENOCEPTORS IN GUINEA‐PIG ATRIA
Author(s) -
Li C. G.,
Rand M. J.
Publication year - 1988
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1988.tb01016.x
Subject(s) - idazoxan , rauwolscine , prazosin , rilmenidine , agonist , chemistry , endocrinology , medicine , quinpirole , stimulation , antagonist , guinea pig , adrenergic receptor , pharmacology , receptor , biology
SUMMARY 1. The present study was carried out to determine whether rilmenidine, a recently introduced antihypertensive agent which acts on α 2 ‐adrenoceptors, has partial agonist activity on prejunctional α 2 ‐adrenoceptors in guinea‐pig atria. 2. Isolated preparations of guinea‐pig atria were incubated with [ 3 H]‐noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as an index of release of transmitter noradrenaline. 3. Rilmenidine (1 μmol/1) inhibited noradrenaline release evoked by short trains (five, 20 and 50 pulses) of sympathetic nerve stimulation and this inhibitory effect of rilmenidine was antagonized by the α 2 ‐adrenoceptor antagonists, idazoxan (0.1 and 0.3 umol/1) and rauwolscine (0.3 umol/1) whereas it was not affected by the α 1 ‐adrenoceptor antagonist prazosin (0.1 μmol/1). 4. On the other hand, rilmenidine (1 μmol/1) enhanced noradrenaline release evoked by long trains (150 and 300 pulses) of stimulation and this effect was also abolished by idazoxan (0.1 μmol/1). 5. These findings suggest that the effects of rilmenidine on transmitter release depend on the degree of auto‐inhibition: when the concentration of noradrenaline in the biophase of the prejunctional α 2 ‐adrenoceptors is low, rilmenidine acts as an agonist, but when the concentration is high it acts as an antagonist. Thus, rilmenidine, like clonidine, is a partial agonist on prejunctional α 2 ‐adrenoceptors in guinea‐pig atria.