A 5-HT1B receptor inverse agonist
SB-224289 hydrochloride is a selective 5-HT1B receptor antagonist, with anxiolytic effect.
SB-224289 has specific toxin-blocking ability and does not inhibit Cho1p. SB-224289 (100 μM-25 μM) shows consistent efficacy at producing Pap-A resistance. SB-224289 does not directly inhibit the PS synthase enzyme in this in vitro assay. Moreover, SB-224289 specifically blocks the activity of papuamides and not other membrane disruptors. SB-224289 is unable to protect wild-type cells against KF, but it is able to provide protection against TPap-A[1]. SB-224289 has a pKi of 8 at human cloned 5-HT1B receptors and displays more than 80 fold selectivity over the closely related 5-HT1D receptor and a range of other receptors. SB-224289 is a potent antagonist with pEC50 of 7.9±0.1. SB-224289 evokes a parallel rightward shift in the 5-HT concentration response curve with pA2 of 8.4±0.2. SB-224289 (100 nM and 1 μM) also significantly increases [3H]-5HT release in electrically stimulated guinea-pig brain cortex slices[3].
SB-224289 (SB 224289) alone or in combination with cocaine, increases anxiety-like behavior. SB 224289 significantly reduces the amount of locomotor activity in the cocaine-treated rats. SB 224289-treated animals spend a significantly longer time in the corners than those treated with vehicle[2]. SB 224289 is a potent antagonist with an ED50 of 3.6 mg/kg, p.o in SK&F-99101-induced hypothermia in the guinea-pig. SB 224289 (4 mg/kg, p.o) reverses sumatriptan-induced inhibition of 5-HT release showing that it is also a potent terminal 5-HT autoreceptor antagonist in vivo. SB 224289 (2-16 mg/kg, p.o) does not increase 5-HT levels in the fuinea-pig frontal cortex. However, SB 224289 (4 mg/kg, p.o) causes a significantly increase in levels of 5-HT in the fuinea-pig dentate gyrus[3].
参考文献:
[1]. Cassilly CD, et al. SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A. PLoS One. 2016 May 16;11(5):e0154932.
[2]. Hoplight BJ, et al. The effects of SB 224289 on anxiety and cocaine-related behaviors in a novel object task. Physiol Behav. 2005 Apr 13;84(5):707-14. Epub 2005 Apr 13.
[3]. Gaster LM, et al. The selective 5-HT1B receptor inverse agonist SB-224289, potently blocks terminal 5-HT autoreceptor function both in vitro and in vivo. Ann N Y Acad Sci. 1998 Dec 15;861:270-1.
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Animal experiment: |
Ninety minutes before each animal is tested, it receives an ip injection of either 5 mg/kg SB 224289 in a vehicle of 10% Trappsol in sterile water or vehicle alone (total volume 1 mL/kg). This dosage of this drug is effective as a pharmacological agent. The rat is put back in its home cage until just before it is to be tested. |
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参考文献: [1]. Cassilly CD, et al. SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A. PLoS One. 2016 May 16;11(5):e0154932. |
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