A selective antagonist of CB1
Ki: 7.8 and 7,9 nM for CB1 and peripheral cannabinoid (CB2), respectively
(S)-SLV 319 is a CB1 receptor antagonist.
It has been reported that central cannabinoid (CB1) receptor antagonists may have potential in the treatment of a variety of diseases including cognitive disorders, neuro-inflammatory disorders, obesity, septic shock, psychosis, addiction, as well as gastrointestinal disorders.
In vitro: Previous study found that (S)-SLV 319 was a potent and selective CB1 receptor antagonist with Ki values of 7.8 and 7,9 nM for CB1 and CB2, respectively. In addition, (S)-SLV 319 was found to be less lipophilic and thus more water soluble than other previously identified ligands of CB1 receptor [1].
In vivo: Previous animal study showed that in rats exposed to an ambient temperature of 22°c, a moderate dose of LPS at 25 - 100 μg/kg could induce a fall in body temperature. Such response was not affected by desensitization of intra-abdominal TRPV1 receptors with resiniferatoxin at 20 μg/kg, by systemic TRPV1 antagonism with capsazepine at 40 mg/kg, or by systemic CB2 receptor antagonism with SR144528 at 1.4 mg/kg. In contrast, CB1 receptor antagonism by SLV319 at 15 mg/kg or rimonabant at 4.6 mg/kg was able to block LPS caused hypothermia [2].
Clinical trial: So far, no clinical study has been conducted.
参考文献:
[1] J.? H. M. Lange, H. H. van Stuivenberg, W. Veerman, et al. Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity. Bioorganic & Medicinal Chemistry Letters 15, 4794-4798 (2005).
[2] Steiner AA et al.? The hypothermic response to bacterial lipopolysaccharide critically depends on brain CB1, but not CB2 or TRPV1, receptors. J Physiol. 2011 May 1;589(Pt 9):2415-31.
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