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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Antagonism of 5-hydroxytryptamine receptors by quipazine.

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 mumol 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 microM 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 microM depressed responses to 5-HT by 75% on average. The threshold concentration for the blocking action was around 0.01 microM, which depressed responses by 42% on average in 6 experiments (range 0 to 75%). 3 5-HT (1 microM or 100 microM) 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 microM), 5-HT (1 microM or 100 microM) 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 microM) shifted the concentration-response curve to the right and depressed the maximum, suggesting a non-competitive mode of antagonism. pI50 values were calculated in order to assess the antagonist activity of quipazine at rat fundus 5-HT receptors; the mean pI50 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.[1]


  1. Antagonism of 5-hydroxytryptamine receptors by quipazine. Lansdown, M.J., Nash, H.L., Preston, P.R., Wallis, D.I., Williams, R.G. Br. J. Pharmacol. (1980) [Pubmed]
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