ライフサイエンスコーパス: salvinorin A

1 ealed similar in vivo effects between 14 and salvinorin A.

2 hat 14 was more metabolically resistant than salvinorin A.

3 from the naturally occurring plant product, salvinorin A.

4 igh binding affinity and agonist efficacy of salvinorin A.

5 mationally restricted compounds derived from salvinorin A.

6 drugs, including ketamine, amphetamine, and salvinorin A.

7 sthetized and treated with the (KOR) agonist salvinorin A (0.01-1.8 mg/kg, i.v.) before administratio

8 Further modification of salvinorin A (1a), the major active component of Salvia

9 nidinonaltrindole, and the diterpene agonist salvinorin A analogue RB-64, reveals both common and dis

10 e-substitution mutagenesis on the binding of salvinorin A and an analogue with a free sulfhydryl grou

11 etamide U-69593, and the non-charged ligands salvinorin A and the octahydroisoquinolinone carboxamide

12 aled that residues known to be important for salvinorin A binding exhibit a differential pattern of w

13 helix 2 are critical for the selectivity of salvinorin A binding to KOR and provide a structurally n

14 We discovered that helix 2 is required for salvinorin A binding to KOR and that two residues (Val-1

15 hat these loci exhibit an indirect effect on salvinorin A binding, presumably through rotation of hel

16 cular, I316, was found to completely abolish salvinorin A binding.

17 e novel insights into the mechanism by which salvinorin A binds to and activates the KOR.

18 f SdCPS2 in catalyzing the committed step in salvinorin A biosynthesis is supported by its biochemica

19 Herein we report the synthesis of several salvinorin A derivatives with modified furan rings.

20 cal characterization of novel, irreversible, salvinorin A-derived ligands suitable as active state pr

21 ial anchoring point for covalent labeling of salvinorin A-derived ligands.

22 B and had similar potency and selectivity to salvinorin A (EC50 = 0.6 +/- 0.2 nM at kappa; >10000 nM

23 Since the finding that salvinorin A exerts its potent psychotropic actions thro

24 The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, i

25 up to 2.5 h post administration, long after salvinorin A had been eliminated from the brain.

26 Importantly, Salvinorin A had no actions at the 5-HT(2A) serotonin re

27 Salvinorin A had no significant activity against a batte

28 In addition, the unique pharmacokinetics of salvinorin A (half-life ~8 min in non-human primates) al

29 gues with substitutions to the furan ring of salvinorin A has prevented a thorough understanding of i

30 More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as

31 vity studies on the neoclerodane diterpenoid salvinorin A have demonstrated the importance of the ace

32 Our initial chemical modifications of salvinorin A have yielded one analogue, herkinorin ( 1c)

33 nged effect on KOR binding but at 0.60 mg/kg salvinorin A induced a sustained decrease in KOR binding

34 Salvinorin A is a naturally occurring hallucinogenic dit

35 Functional studies demonstrated that Salvinorin A is a potent kappa opioid agonist at cloned

36 Salvinorin A is a psychoactive natural product that has

37 Because Salvinorin A is a psychotomimetic selective for kappa op

38 ich has as its endogenous agonist a peptide; salvinorin A is also the only known non-nitrogenous opio

39 ects are particularly remarkable because (1) salvinorin A is the first reported non-nitrogenous opioi

40 The neoclerodane diterpene salvinorin A is the major active component of the halluc

41 Salvinorin A is unique among ligands for peptidergic G p

42 Salvinorin A is unique in that it is the only known lipi

43 The activity of salvinorin A is unusual compared to other opioids such a

44 ive ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint fami

45 The main bioactive metabolite, salvinorin A, is the first non-nitrogenous natural compo

46 cs is considered, micro opioids derived from salvinorin A may offer a unique template for the develop

47 We discovered that Salvinorin A potently and selectively inhibited (3)H-bre

48 The structural basis to salvinorin A recognition of the kappa-opioid receptor is

49 The results show that salvinorin A recognizes a collection of residues in tran

50 Intriguingly, activation of KORs by salvinorin A required interactions with the helix 7 tyro

51 receptor, which has negligible affinity for salvinorin A, revealed that residues known to be importa

52 Its primary active ingredient, Salvinorin A (SA)-a highly selective agonist at the kapp

53 furyl-delta-lactone core similar to that of Salvinorin A (Sal A), another natural product from the p

54 administration of the selective KOR agonist salvinorin A (salvA).

55 elease by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R st

56 Structural modification of salvinorin A, the active component of Salvia divinorum,

57 Salvinorin A, the active component of the hallucinogenic

58 Salvinorin A, the most potent naturally occurring halluc

59 Salvinorin A thus represents, to our knowledge, the firs

60 en together, they imply that the diterpenoid salvinorin A utilizes unique residues within a commonly

61 a binding site model is proposed that aligns salvinorin A vertically within a pocket spanning transme

62 When salvinorin A was administered 1 min prior to injection o

63 Salvinorin A was administered up to 5 h prior to [(11)C]

64 Surprisingly, we discovered that salvinorin A was stabilized in the binding pocket by int

65 r basis for the subtype-selective binding of salvinorin A, we utilized an integrated approach using c