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Pharmacological Characterization of 5-Hydroxytryptamine Receptors in the Gastrointestinal Tract
Published in T.S. Gaginella, J.J. Galligan, SEROTONIN and GASTROINTESTINAL FUNCTION, 2020
Jeremy D. Gale, Keith T. Bunce
Spiperone is the most commonly used antagonist at 5-HT1A receptors, yielding pKi or pKB measurements of approximately 7.5.8,16,17 However, spiperone is a potent antagonist at 5-HT2 receptors (pA2 = 8.6),38 α-adrenoceptors (pA2 = 7.8),38 and at dopamine D2 receptors (pKi = 9.1).39 Another compound of interest is MDL 73005, which in radioligand binding experiments exhibited high affinity for the 5-HT1A binding site (pKi = 8.6).40 The advantage of this compound is a very high degree of selectivity and specificity for 5-HT1A over other receptor subtypes.40 NAN-190 is another useful antagonist that in receptor binding experiments has a pKi for the 5-HT1A receptor of 8.9.41 In some functional systems, measurements of antagonist potency for NAN-190 and MDL 73005 can be underestimated by up to two log units.31 This is thought to result from these compounds being slow to reach equilibrium.42 In a number of studies, both MDL 73005 and NAN-190 demonstrate partial agonist activity43,44 and so should be used with caution. Moreover, NAN-190 has high binding affinity for α1-adrenoceptors (pKi= 8.9)45 and in functional studies was 250 times more potent as an antagonist of α1-adrenoceptor-mediated events than was prazosin.46Table 1 summarizes the drugs used to identify 5-HT1A receptors.
Neuronal and behavioral plasticity: the role of serotonin and BDNF systems tandem
Published in Expert Opinion on Therapeutic Targets, 2019
Nina K. Popova, Vladimir S. Naumenko
The pro-neurogenic effect of 5-HT is mediated, at least partly, by 5-HT1A receptors. The first evidence that 5-HT1A receptor regulates adult neurogenesis came from the study showed the effect of 5-HT1A receptor antagonists on hippocampal neurons . All three 5-HT1A receptor antagonists (NAN-190, p-MPPI, and WAY-100635) reduced cell proliferation in the dentate gyrus of adult rats [52]. A later study with 5-HT1A receptor agonists supported this notion. Chronic treatment with 5-HT1A receptor partial agonists tandospirone [53], 8-OH-DPAT [54,55], clozapine, and aripiprazole [56] increased hippocampal neurogenesis in adult rats. Increased proliferation and survival of newborn cells in dentate gyrus was shown in adult mice with permanent overexpression of postsynaptic 5-HT1A receptors [57]. Critical role of 5-HT1A receptor for antidepressant-induced hippocampal neurogenesis and behavioral response has been also demonstrated using 5-HT1A receptor knockout mice [58,59]. Taken together, these data suggest that postsynaptic 5-HT1A receptors are important player in the neurogenesis and in antidepressive response of adult animals.