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ANTAGONISM OF 5‐HYDROXYTRYPTAMINE RECEPTORS BY QUIPAZINE
Author(s) -
LANSDOWN M.J.R.,
NASH H.L.,
PRESTON P.R.,
WALLIS D.I.,
WILLIAMS R.G.
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb14568.x
Subject(s) - quipazine , serotonin , serotonin agonist , agonist , medicine , endocrinology , chemistry , 5 ht receptor , antagonist , sucrose gap , dorsal root ganglion , receptor , spinal cord , biology , neuroscience , electrophysiology
1 The antagonist actions of quipazine on 5‐hydroxytryptamine (5‐HT) receptors have been investigated in the rabbit isolated superior cervical ganglion and on the rat isolated spinal cord and stomach strip. 2 Changes in membrane potential induced by 5‐HT or by the nicotinic agonist, 1,1‐dimethyl‐4‐phenyl piperazinium (DMPP), were measured in the ganglion by the sucrose‐gap technique. At ganglionic receptors, quipazine had little or no agonist activity, but greatly depressed depolarizations evoked by 5‐HT but not depolarizations evoked by DMPP or trimethylammonium (TMA). Injections into the superfusion stream to the ganglion of 2 to 5 μmol quipazine in a small volume of Krebs solution prevented all subsequent responses to 5‐HT. Superfusion of the ganglion with quipazine at a concentration of 1 μ m produced complete blockade of responses to 5‐HT in 3 of 6 ganglia and reduced responses by over 90% in 2 others; responses to DMPP were potentiated in amplitude and duration. Superfusion at a concentration of 0.1 μ m depressed responses to 5‐HT by 75% on average. The threshold concentration for the blocking action was around 0.01 μ m , which depressed responses by 42% on average in 6 experiments (range 0 to 75%). 3 5‐HT (1 μ m or 100 μ m ) depressed the amplitude of the dorsal root potentials recorded from the isolated, hemisected cord of the neonate rat by 27 ± 5% (mean ± s.e. mean, n = 14) and by 45 ± 6% ( n = 14), respectively. In the presence of quipazine (0.01 μ m ), 5‐HT (1 μ m or 100 μ m ) depressed the amplitude by 6 ± 2% ( n = 15) and by 3 ± 1% ( n = 7), respectively. 4 Concentration‐response curves of the contractions induced by 5‐HT in the fundus of the rat stomach were obtained in the absence and presence of quipazine. Quipazine (1 μ m ) shifted the concentration‐response curve to the right and depressed the maximum, suggesting a non‐competitive mode of antagonism. pI 50 values were calculated in order to assess the antagonist activity of quipazine at rat fundus 5‐HT receptors; the mean pI 50 was 6.91 ± 0.2 ( n = 6). 5 It is concluded that quipazine may be an effective antagonist at 5‐HT receptors in various tissues.