ライフサイエンスコーパス: FAAH

1 FAAH bound alphaGalCer in vivo and in vitro and was requ

2 FAAH inactivation promotes beneficial effects upon pain

3 FAAH inhibition, however, does not increase PEA levels i

4 FAAH inhibitors have shown analgesic and antiinflammator

5 FAAH inhibitors may be useful in treating many disorders

6 FAAH Pro129/Pro129 homozygotes, who constitute nearly ha

7 FAAH(-/-) mice were also prone to diet-induced hepatic i

8 FAAH-IR was also present in small, NF200-negative cultur

9 grading enzyme fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT),

10 Pretreatments with a FAAH inhibitor demonstrated that 80-95% of brain uptake

11 Thus, the AEA/FAAH pathway is an important mediator of HPV and is invo

12 Nearly all FAAH inhibitors known to date attain their binding poten

13 ability of acute stress to modulate amygdala FAAH and AEA in both rats and mice is also mediated thro

14 otype accompanied by elevations in amygdalar FAAH activity and reduced dialysate N-arachidonoylethano

15 In the presence of 100 nM URB597, an FAAH inhibitor, the effect of 10 nM AEA on outflow facil

16 Treatment with an FAAH inhibitor relieves sensitized glutamatergic respons

17 sms associated with differential anandamide (FAAH rs324420) and CRF1 (CRHR1 rs110402) signaling modul

18 amined the influence of dysregulated CRF and FAAH systems in altering excitatory transmission in the

19 We have recently discovered that MAGL and FAAH are both inhibited by carbamates bearing an N-piper

20 indings support the idea that joint MAGL and FAAH inhibition represents a promising approach for the

21 tudying the endogenous functions of MAGL and FAAH.

22 gnificance of these metabolites in vivo, and FAAH mutants may offer opportunities to address this in

23 als were detected on TM tissues with an anti-FAAH antibody.

24 Recently, an Arabidopsis FAAH homologue (AtFAAH) was identified, and several stud

25 ancing the enzymatic activity of Arabidopsis FAAH (AtFAAH).

26 In homogenate activity assays, FAAH-2 hydrolyzed AEA and palmitoylethanolamide (PEA) wi

27 and second-generation O-arylcarbamate-based FAAH inhibitors, URB597 (cyclohexyl carbamic acid 3'-car

28 Both FAAH inhibitors: (1) blocked FAAH activity in brain and liver, increasing levels of e

29 od and brain FAAH inhibition, allowing blood FAAH activity to be used as a target biomarker.

30 Both FAAH inhibitors: (1) blocked FAAH activity in brain and

31 nterestingly, those where disruption of both FAAH and MAGL produced additive effects that were revers

32 s in the potency and selectivity toward both FAAH and MAGL.

33 Brain FAAH binding was measured with positron emission tomogra

34 Although brain FAAH may be the relevant target for inhibition, rat stud

35 s show a correlation between blood and brain FAAH inhibition, allowing blood FAAH activity to be used

36 However, the status of brain FAAH in cannabis use disorder is unknown.

37 muM; IC(50) (30) = 0.68 muM), and rat brain FAAH (IC(50) (8) = 5.1 muM; IC(50) (30) = 0.29 muM).

38 Anandamide is degraded by FAAH and primarily works by activating two G-protein-cou

39 es an anxious phenotype that is prevented by FAAH inhibition.

40 This was reversed by FAAH inhibitors or exogenous NAE substrate.

41 the reactivation mechanism of carbamoylated FAAH is investigated by means of a quantum mechanics/mol

42 Complete FAAH inhibition blocks only a subset of withdrawal signs

43 and Cox-2 (median inhibitory concentration: FAAH, 0.031 +/- 0.002 microM; Cox-1, 0.012 +/- 0.002 mic

44 In contrast, FAAH-2 hydrolyzed AEA and PEA in intact cells with rates

45 ransmission in the CeA, and dysregulated CRF-FAAH facilitates stress-induced increases in glutamaterg

46 d increased hepatic AEA levels and decreased FAAH activity are absent in SCD1(-/-) mice, and the mono

47 andidate inhibitors exhibited time-dependent FAAH inhibition and noncompetitive irreversible inactiva

48 e developed a subset of nanomolar dialyzable FAAH inhibitors (5v-z), functionalized by specific polye

49 SLC6A3, BDNF, SLC6A4, CSNK1E, SLC6A2, DRD2, FAAH, COMT, OPRM1).

50 s 9 and 19 were identified as effective dual FAAH/ChE inhibitors, with well-balanced nanomolar activi

51 nesterase system, and achieve effective dual FAAH/cholinesterase inhibitors.

52 we describe a selective and efficacious dual FAAH/MAGL inhibitor, JZL195, and show that this agent ex

53 inhibitor JZL184, as well as the novel dual FAAH-MAGL inhibitor SA-57, which is 100-fold more potent

54 nformation that may guide the design of dual FAAH-COX inhibitors with superior analgesic efficacy.

55 was drug discrimination behavior, where dual FAAH/MAGL blockade, but not disruption of either FAAH or

56 Elevations in CRF-CRF1 signaling dysregulate FAAH activity, and this genotypic difference is normaliz

57 Moreover, either FAAH(-/-) mice or wild-type mice treated with FAAH inhib

58 /MAGL blockade, but not disruption of either FAAH or MAGL alone, produced THC-like responses that wer

59 t diet-derived MUFAs, function as endogenous FAAH inhibitors mediating the HFD-induced increase in he

60 w compounds have been described that enhance FAAH activity.

61 Collectively, these results establish FAAH-2 as a bone fide NAE-catabolizing enzyme and sugges

62 providing new insights that help to explain FAAH's interaction with substrate leaving groups and the

63 ysis were examined in COS-7 cells expressing FAAH restricted to the endoplasmic reticulum, mitochondr

64 tent with this, carriers of a low-expressing FAAH variant (385A allele; rs324420) exhibited quicker h

65 re observed in COS-7 cells stably expressing FAAH.

66 Lipid droplet localization was essential for FAAH-2 activity as chimeras excluded from lipid droplets

67 that the compound is a covalent modifier for FAAH and inhibits its action in an irreversible manner.

68 ut lines, have suggested an in vivo role for FAAH in the catabolism of NAEs in plants.

69 ed or enhanced the intrinsic selectivity for FAAH versus other serine hydrolases.

70 aurine [NAT(20:0)]-as primary substrates for FAAH in mouse skin, and show that the levels of these su

71 tudy was to determine whether combined, full FAAH inhibition and partial MAGL represents an optimal s

72 mice pure oleic acid fail to inhibit hepatic FAAH activity.

73 events the diet-induced reduction of hepatic FAAH activity, normalizes hepatic AEA levels, and improv

74 Using recombinant rat and human FAAH, we show that 5-(4-hydroxyphenyl)pentanesulfonyl fl

75 750), that shows strong preference for human FAAH.

76 the inhibitor sensitivity profiles of human FAAH but maintains the high-expression yield of the rat

77 s not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the ob

78 ered by difficulties in expressing the human FAAH enzyme.

79 we hypothesized that variation in the human FAAH gene would predict individual differences in amygda

80 in the gene for fatty acid amide hydrolase (FAAH) (C385A; rs324420), the primary catabolic enzyme fo

81 n an increase in fatty acid amide hydrolase (FAAH) activity and a reduction in the concentration of t

82 A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analog

83 ctivity at human fatty acid amide hydrolase (FAAH) and dopamine receptor subtype D3 (D3R).

84 1) function; and fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (N

85 nized variant of fatty acid amide hydrolase (FAAH) are disclosed and comparatively discussed alongsid

86 ipase (MAGL) and fatty acid amide hydrolase (FAAH) are two enzymes from the serine hydrolase superfam

87 lipase (MAGL) or fatty acid amide hydrolase (FAAH) attenuates naloxone-precipitated opioid withdrawal

88 on of the enzyme fatty acid amide hydrolase (FAAH) counteracts reward-related effects of nicotine in

89 Fatty acid amide hydrolase (FAAH) degrades NAE into ethanolamine and free fatty acid

90 Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which att

91 or hydrolyzed by fatty acid amide hydrolase (FAAH) during normal seedling establishment, and this con

92 lated the enzyme fatty acid amide hydrolase (FAAH) from mouse serum as an alphaGalCer-binding protein

93 ses, among which fatty acid amide hydrolase (FAAH) has been well characterized.

94 membrane enzyme fatty acid amide hydrolase (FAAH) hydrolyzes the endocannabinoid anandamide and rela

95 e 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volu

96 nd that both the fatty acid amide hydrolase (FAAH) inhibitor URB597 and the synthetic cannabinoid ago

97 infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA

98 rally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3'-ca

99 ue 3 as a potent fatty acid amide hydrolase (FAAH) inhibitor.

100 -ketoheterocycle fatty acid amide hydrolase (FAAH) inhibitors are disclosed that additionally and irr

101 rtant classes of fatty acid amide hydrolase (FAAH) inhibitors that carbamoylate the active-site nucle

102 Fatty acid amide hydrolase (FAAH) is a degradative enzyme for a group of endogenous

103 these lipids by fatty acid amide hydrolase (FAAH) is a key regulatory point in NAE signaling activit

104 Fatty acid amide hydrolase (FAAH) is one of the main enzymes responsible for the deg

105 Fatty acid amide hydrolase (FAAH) knockout mice are prone to excess energy storage a

106 olized by either fatty acid amide hydrolase (FAAH) or by lipoxygenase (LOX) to low levels during seed

107 letion of either fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), enzymes that re

108 Fatty acid amide hydrolase (FAAH) plays a key role in regulating the tone of the end

109 s CNR1 rs806378, fatty acid amide hydrolase (FAAH) rs324420, and MGLL rs4881.

110 Fatty acid amide hydrolase (FAAH) terminates the endocannabinoid signaling pathway t

111 as inhibitors of fatty acid amide hydrolase (FAAH) that additionally target the cytosolic port Cys269

112 t mice devoid of fatty acid amide hydrolase (FAAH) with elevated levels ofN-arachidonyl ethanolamide

113 ) cells, whereas fatty acid amide hydrolase (FAAH)(-/-) mice, which have elevated levels of AEA, yiel

114 Fatty acid amide hydrolase (FAAH), a gene in the minimal subcongenic interval genera

115 and 2) bound to fatty acid amide hydrolase (FAAH), a key enzymatic regulator of endocannabinoid sign

116 ethanolamine via fatty acid amide hydrolase (FAAH), although it is unclear whether chronic dysregulat

117 Fatty acid amide hydrolase (FAAH), an amidase-signature family member, is an integra

118 is hydrolyzed by fatty acid amide hydrolase (FAAH), an enzyme localized on the endoplasmic reticulum.

119 is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as po

120 is by 2 enzymes: fatty acid amide hydrolase (FAAH), and the less-studied N-acylethanolamine-hydrolyzi

121 selectivity over fatty acid amide hydrolase (FAAH), another endocannabinoid-hydrolyzing enzyme.

122 serve this role: fatty acid amide hydrolase (FAAH), cyclooxygenase-2 (COX-2), monoacylglycerol lipase

123 serine amidase, fatty acid amide hydrolase (FAAH), degrades a heterogeneous family of lipid-derived

124 zymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamin

125 itor (URB937) of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of the

126 the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, o

127 polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) lev

128 on of the enzyme fatty acid amide hydrolase (FAAH), which causes a reduction in the endocannabinoid a

129 iction (HPV) via fatty acid amide hydrolase (FAAH)-dependent metabolites.

130 properties, and fatty acid amide hydrolase (FAAH)-mediated hydrolysis is a primary catabolic pathway

131 degrading enzyme fatty acid amide hydrolase (FAAH).

132 damide hydrolase fatty acid amide hydrolase (FAAH).

133 catabolic enzyme fatty acid amide hydrolase (FAAH).

134 membrane enzyme fatty acid amide hydrolase (FAAH).

135 ivo inhibitor of fatty acid amide hydrolase (FAAH).

136 X-1), COX-2, and fatty acid amide hydrolase (FAAH).

137 ipase (MAGL) and fatty acid amide hydrolase (FAAH).

138 degrading enzyme fatty acid amide hydrolase (FAAH).

139 ed by the enzyme fatty acid amide hydrolase (FAAH).

140 dation of AEA by fatty acid amide hydrolase (FAAH).

141 catabolic enzyme fatty acid amide hydrolase (FAAH).

142 se by the enzyme fatty acid amide hydrolase (FAAH).

143 Fatty acid amide hydrolase (FAAH, EC 3.5.1.99) is the main enzyme catabolizing endoc

144 Brain-impenetrant FAAH inhibitors, which strengthen this gating mechanism,

145 l ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date.

146 of inhibitor series, simultaneously improves FAAH potency and selectivity and can provide exquisitely

147 es are needed to examine possible changes in FAAH binding during prolonged cannabis abstinence and wh

148 nd function were absent in mice deficient in FAAH.

149 were depleted during seedling growth even in FAAH tDNA knock-out plants.

150 e we show that reduced energy expenditure in FAAH(-/-) mice could be attributed to decreased circulat

151 lmonary arteries and strongly reduced HPV in FAAH(-/-) mice and wild-type mice upon pharmacological t

152 NAE-oxylipin metabolites were identified in FAAH fatty acid amide hydrolase seedlings but not in wil

153 greatly improved bioluminescence imaging in FAAH-expressing tissues such as the brain.

154 An increase in FAAH mRNA and enzyme activity in dorsal root ganglia (DR

155 oncerning the role of this water molecule in FAAH's catalytic mechanism, we determined the structure

156 storage and adiposity, whereas mutations in FAAH are associated with obesity in humans.

157 ests DRG neurons contribute to the increased FAAH activity in skin in tumor-bearing mice.

158 of SCD1, palmitoleic and oleic acid, inhibit FAAH activity in vitro at low micromolar concentrations.

159 d persist in the brain to completely inhibit FAAH for a prolonged period.

160 ly active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity

161 ototype 4: (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration:

162 h and remain active in the brain, inhibiting FAAH for a sustained period.

163 which is 100-fold more potent in inhibiting FAAH than MAGL, would prevent spontaneous withdrawal in

164 ed to assess the effects of NAAA inhibition, FAAH inhibition, and PEA on macroscopic signs of colon i

165 tive (IR) DRG neurons ipsilateral to injury: FAAH immunoreactivity was detected in larger-sized cells

166 Molecular shape overlay of 3 with a known FAAH inhibitor indicated that these compounds might act

167 Building on experience with a rat leukocyte FAAH activity assay using [(3)H]AEA, we have developed a

168 contrast to endoplasmic reticulum-localized FAAH, immunofluorescence revealed FAAH-2 was localized o

169 Lower FAAH binding levels in the brain may be a consequence of

170 longed cannabis abstinence and whether lower FAAH binding predates drug use.

171 can be tuned for MAGL-selective or dual MAGL-FAAH inhibition by the attachment of an appropriately su

172 y new pharmacological tools for manipulating FAAH- and NAE-mediated physiological processes in plants

173 seful pharmacological tools for manipulating FAAH-mediated regulation of NAE signaling in plants or a

174 inhibitors opens a new avenue for modulating FAAH activity through nonmechanism-based inhibition.

175 dronabinol reduces fasting colonic motility; FAAH and CNR1 variants could influence the effects of th

176 Multitarget FAAH/Cox blockade may provide a transformative approach

177 pounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature an

178 zimidazoles as unique and potent noncovalent FAAH inhibitors.

179 ethanolamides act to enhance the activity of FAAH and may stimulate the turnover of NAEs in vivo.

180 as used to measure the enzymatic activity of FAAH in TM tissue.

181 dy reveals the existence and the activity of FAAH, an AEA-metabolizing enzyme, in the TM tissues.

182 phism impacts the expression and activity of FAAH, thereby increasing anandamide levels.

183 their effects on the hydrolytic activity of FAAH.

184 ck out and pharmacological administration of FAAH inhibitors in rodent models result in analgesic, an

185 performed a biochemical characterization of FAAH-2 and explored its capacity to hydrolyze NAEs in ce

186 ated and compared to that for deacylation of FAAH acylated by the substrate oleamide.

187 tial energy surfaces for decarbamoylation of FAAH covalent adducts, derived from the O-aryl carbamate

188 ve and selective bioluminescent detection of FAAH activity in vitro, in live cells, and in vivo.

189 hat genetic or pharmacological disruption of FAAH activity accelerates skin wound healing in mice and

190 The potency and tissue distribution of FAAH inhibitors can be imaged in live mice, and luciferi

191 tward shift in the cell-size distribution of FAAH-immunoreactive (IR) DRG neurons ipsilateral to inju

192 Further, the anti-anxiety effect of FAAH deletion was recapitulated in rats treated orally w

193 The effects of FAAH inhibition on nicotine self-administration and nico

194 analysis was used to study the expression of FAAH, and a thin-layer chromatography-based approach was

195 y reflect an alteration of the expression of FAAH, thus forming the basis for the rational design of

196 table radiotracer for the in vivo imaging of FAAH using PET.

197 Inhibition of FAAH activity increases AEA concentrations in nervous ti

198 hese inhibitors achieve potent inhibition of FAAH activity primarily from shape complementarity to th

199 ta support the hypothesis that inhibition of FAAH has therapeutic potential in the treatment of anxie

200 nd rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancemen

201 used to profile the successful inhibition of FAAH in recent clinical trials.

202 Pharmacological inhibition of FAAH reversed the increase in receptor revision, RAG exp

203 t exhibit potent and selective inhibition of FAAH.

204 ly with a novel pharmacological inhibitor of FAAH, JNJ5003 (50 mg per kg per day), during exposure to

205 Several active site-directed inhibitors of FAAH have been identified, but few compounds have been d

206 In animals, chemical inhibitors of FAAH have been used for therapeutic treatment of pain an

207 were prepared and examined as inhibitors of FAAH.

208 s that they raise endogenous brain levels of FAAH substrates to a greater extent and for a much longe

209 This study reveals the location of FAAH in neural tissue involved in peripheral nociceptive

210 r findings identify not only the presence of FAAH in normal mouse serum, but also its critical role i

211 probe deeper into biochemical properties of FAAH.

212 increase in both the size and proportion of FAAH-IR DRG occurred after spinal nerve transection inju

213 fasting distal MI in patients, regardless of FAAH rs324420 variant (CA/AA vs CC) (P = .046); the grea

214 he putative N-terminal hydrophobic region of FAAH-2 was identified as a functional lipid droplet loca

215 reducing the negative feedback regulation of FAAH activity by free ethanolamine.

216 ntify key residues within the active site of FAAH that confer the species-specific sensitivity to inh

217 valent inhibitor, the cocrystal structure of FAAH complexed with compound 2 reveals that these ketobe

218 ic mechanism, we determined the structure of FAAH conjugated to a urea-based inhibitor, PF-3845, to a

219 The X-ray structure of FAAH in complex with the NSAID carprofen, along with sit

220 yl groups, providing the first structures of FAAH bound to an inhibitor as a deprotonated hemiketal m

221 lls with rates approximately 30-40% those of FAAH, highlighting a potentially greater contribution to

222 proximately 6 and approximately 20% those of FAAH, respectively.

223 genous or endogenous cannabinoids and use of FAAH inhibitors may constitute novel therapeutic modalit

224 hydrolase seedlings but not in wild-type or FAAH overexpressors, suggesting that NAE hydroxide pools

225 ogenous brain levels of anandamide and other FAAH substrates upon intraperitoneal (i.p.) administrati

226 Importantly, the assay preserved partial FAAH inhibition resulting from ex vivo treatment with a

227 mmon catalytic mechanism in animal and plant FAAH enzymes.

228 can provide exquisitely selective and potent FAAH inhibitors.

229 We have synthesized a series of potent FAAH inhibitors encompassing two classes of N-alkyl-O-ar

230 ed in vitro and ex vivo in rats as potential FAAH imaging agents for positron emission tomography (PE

231 iotracers are required to image and quantify FAAH activity in vivo.

232 The resulting humanized rat (h/r) FAAH protein exhibits the inhibitor sensitivity profiles

233 ive amino acids known to be critical for rat FAAH activity are also conserved in AtFAAH (Lys-205, Ser

234 ure of 3 bound to a humanized variant of rat FAAH revealed that 3 was not only covalently bound to th

235 In naive rats, FAAH immunoreactivity localized to the soma of 32.7 +/-

236 Recently, FAAH-2 was discovered in humans, suggesting an additiona

237 (JZP-327A, 51), inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 nM),

238 s increased the apparent Vmax of recombinant FAAH proteins from both plant (Arabidopsis) and mammalia

239 Specifically, there is reduced FAAH expression associated with the variant allele that

240 1, 2, 4, 5 down-regulated FAAH mRNA expression.

241 ced damage through a mechanism that requires FAAH inhibition.

242 rins CycLuc1 and CycLuc2 or their respective FAAH-sensitive luciferin amides.

243 ated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylca

244 -localized FAAH, immunofluorescence revealed FAAH-2 was localized on lipid droplets.

245 A 10-2474, an orally administered reversible FAAH inhibitor, was given to healthy volunteers to asses

246 emely potent, noncompetitive, and reversible FAAH inhibitors endowed with a remarkable selectivity pr

247 experimental data showing slowly reversible FAAH inhibition for the N-piperazinylurea inhibitor and

248 thermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of huma

249 ents employing a novel, potent and selective FAAH inhibitor, AM3506 (5-(4-hydroxyphenyl)pentanesulfon

250 Exceptionally potent and selective FAAH inhibitors emerged from the series (e.g., 6, Ki = 2

251 3,4-oxadiazol-2-ones as potent and selective FAAH inhibitors has been described.

252 Aiming at discovering new selective FAAH inhibitors, we developed a series of compounds (5a-

253 Comparison of JZL195 to specific FAAH and MAGL inhibitors identified behavioral processes

254 URB937 suppressed FAAH activity and increased anandamide levels outside th

255 icate for whom and for what anxiety symptoms FAAH inhibitors or exposure-based therapies will be most

256 tegies for cannabis use disorder that target FAAH and endocannabinoids.

257 Targeting FAAH activity, therefore, presents a promising new thera

258 atty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), that lacked ami

259 45, a highly selective and clinically tested FAAH inhibitor.

260 the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-24

261 , may lead to systemic autoimmunity and that FAAH is a lupus-susceptibility gene that might regulate

262 We previously found that FAAH and COX-2 do not have a role in determining the dur

263 Our data indicate that FAAH deletion, and the resulting increases in NAEs, pred

264 Collectively, these studies indicate that FAAH-mediated decreases in AEA occur following chronic s

265 These data suggest that FAAH inhibitors may represent a novel class of anxiolyti

266 These studies suggest that FAAH is required for chronic stress to induce hyperactiv

267 Our data suggest that FAAH overexpression alters phytohormone accumulation and

268 The FAAH genetic polymorphism (rs324420) and blood, urine, a

269 The FAAH selectivity of the compound 51 over the supposed ma

270 nts revealed a clear increase of AEA and the FAAH-dependent metabolite arachidonic acid in hypoxic lu

271 s that had shown promising activities at the FAAH-D3R target combination in preliminary studies.

272 herein, emerge from both enhancements in the FAAH activity and simultaneous disruption of binding aff

273 A mutation in the FAAH gene that enhances endocannabinoid signaling has be

274 ,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that

275 tion-PCR, we demonstrate the location of the FAAH in adult rat DRG, sciatic nerve, and spinal cord.

276 combined administration of high-dose of the FAAH inhibitor PF-3845 and low-dose of the MAGL inhibito

277 iscrimination procedures, and neither of the FAAH inhibitors induced dopamine release in the nucleus

278 Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environm

279 Here, we report the structure of the FAAH-URB597 complex at 2.3 A resolution.

280 ng the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amy

281 mong IBS with constipation patients with the FAAH CC variant (P = .045).

282 Incubation of these cultures with the FAAH inhibitor URB597 increased AEA-evoked cobalt uptake

283 ce in response to chronic treatment with the FAAH inhibitor URB597.

284 noid signaling to therapeutic levels through FAAH inhibition might be beneficial for neurodegenerativ

285 he enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase

286 s, suggesting that trafficking of [3H]AEA to FAAH had been disrupted.

287 traction measurements showed that binding to FAAH was irreversible and kinetically different for the

288 serine hydrolases that are non-homologous to FAAH, such as elastase, trypsin, or chymotrypsin, shows

289 er 2 indicates that they bind identically to FAAH, albeit with reversed orientations of the central a

290 to transport AEA from the plasma membrane to FAAH for inactivation and may therefore be novel pharmac

291 The results point to FAAH-regulated NAT signaling as an unprecedented lipid-b

292 y constituted binding of the radiotracers to FAAH.

293 In cannabis users, FAAH binding was significantly lower by 14%-20% across t

294 ith diarrhea or alternating with the variant FAAH CA/AA (P = .013).

295 However, the molecular mechanism by which FAAH affects energy expenditure (EE) remains unknown.

296 proach to IBD and other pathologies in which FAAH and Cox are overactive.

297 st that Arabidopsis LOXs indeed compete with FAAH to metabolize PU-NAEs during seedling establishment

298 ound unique to this class of inhibitors with FAAH.

299 AAH(-/-) mice or wild-type mice treated with FAAH inhibitor URB597 are protected against hypoxia-indu

300 ype mice upon pharmacological treatment with FAAH inhibitor URB597.