ライフサイエンスコーパス: allopregnanolone

1 xy-5alpha-pregnan-20-one (3alpha,5alpha-THP; allopregnanolone).

2 tor finasteride, as well as progesterone and allopregnanolone.

3 ely catalyzes the intracellular oxidation of allopregnanolone.

4 ersion of progesterone into the neurosteroid allopregnanolone.

5 to synthesize 5alpha-dihydroprogesterone and allopregnanolone.

6 re observed for estradiol, progesterone, and allopregnanolone.

7 nol, t-butanol, pentobarbital, diazepam, and allopregnanolone.

8 e modulator DHEAS and the positive modulator allopregnanolone.

9 s were markedly prolonged in the presence of allopregnanolone.

10 eous formulation of the neuroactive steroid, allopregnanolone.

11 s including sensitivity to the neurosteroid, allopregnanolone.

12 with EC50 values similar to those found for allopregnanolone.

13 r a combination of clonazepam with exogenous allopregnanolone.

14 Finally, PPI deficits were exacerbated by allopregnanolone (10 mg/kg, IP) and attenuated by proges

15 rents were also enhanced by the neurosteroid allopregnanolone (10 nM).

16 um, cultures were exposed to DHEA, DHEAS, or allopregnanolone (10(-10), 10(-8), or 10(-6) M), or vehi

17 roid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, 3 alpha, 5 alpha-TH PROG).

18 that the neuroactive progesterone metabolite allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one)

19 Of 20 NAS tested, allopregnanolone, (3alpha,5alpha,20E)-3-hydroxy-13,24-cy

20 e mutations could not confer potentiation by allopregnanolone (3alpha5alphaP) when expressed in recep

21 ceptor modulation by the endogenous steroids allopregnanolone (3alpha5alphaP), pregnenolone sulfate,

22 of (3alpha,5alpha)-3-hydroxypregnan-20-one (allopregnanolone, 3alpha5alphaP).

23 Among these steroids, however, only allopregnanolone (5-15 mg/kg, IP) dose-dependently exace

24 quantitative method for the determination of allopregnanolone (5alpha,3alpha-THP) and related neurost

25 Here we show that THP (allopregnanolone), a steroid that is released as a resul

26 ulates opioid production in the brainstem is allopregnanolone, a neurosteroid metabolite of progester

27 47 injection), an intravenous formulation of allopregnanolone, a positive allosteric modulator of gam

28 yl-3-hydroxybutyryl-CoA and the oxidation of allopregnanolone, a positive modulator of the gamma-amin

29 d and unsulfated steroids, such as DHEAS and allopregnanolone, act at distinct sites implies that ste

30 This novel opioid-mediated mechanism of allopregnanolone action may alter regulation of other br

31 The neurosteroid allopregnanolone acts as a positive allosteric modulator

32 3alpha-hydroxysteroid-5alpha-pregnan-20-one (allopregnanolone) acts as a positive allosteric modulato

33 A single neonatal allopregnanolone administration (10 mg/kg, i.p.) was pre

34 We investigated whether neonatal allopregnanolone administration alters the neuronal popu

35 These findings suggest that neonatal allopregnanolone administration disrupts the normal deve

36 ct of acute ethanol administration and acute allopregnanolone administration on spontaneous hippocamp

37 decreased in the medial dorsal nucleus after allopregnanolone administration.

38 Interestingly, mice treated with allopregnanolone after MPTP lesion were able to perform

39 We show that the neurosteroid allopregnanolone (ALLO) and T0901317, a synthetic oxyste

40 Allopregnanolone (ALLO) and tetrahydrodeoxycorticosteron

41 gression associated with a decrease of brain allopregnanolone (Allo) content and a decrease (approxim

42 ard intruders and a down-regulation of brain allopregnanolone (Allo) content.

43 ctase type I (5alpha-RI) mRNA expression and allopregnanolone (Allo) levels in selected neurons of th

44 ated with a down-regulation of telencephalic allopregnanolone (Allo) levels.

45 The progesterone derivative allopregnanolone (ALLO) rapidly potentiates gamma-aminob

46 Allopregnanolone (ALLO), is a brain endogenous neuroster

47 Allopregnanolone (ALLO), synthesized by pyramidal neuron

48 Allopregnanolone also evoked dose-dependent anesthetic a

49 We hypothesized that serum allopregnanolone and 3alpha-androstanediol levels would

50 rosteroids can reduce HPA axis responses, so allopregnanolone and 3beta-androstanediol (3beta-diol; 5

51 d 5alpha-DHP reduction yielded two products, allopregnanolone and 5alpha,20alpha-tetrahydroprogestero

52 ntiomers (pregnanolone and ent-pregnanolone, allopregnanolone and ent-allopregnanolone) and show that

53 pregnenolone following a swim stress and for allopregnanolone and epiallopregnanolone following allop

54 sults further demonstrate similar effects of allopregnanolone and ethanol on hippocampal neurophysiol

55 [(3)H]flunitrazepam as radioligand in which allopregnanolone and its active analogues stimulated the

56 d an increase in [Ca2+]i in response to both allopregnanolone and muscimol.

57 001) were observed in the frontal cortex for allopregnanolone and pregnenolone following a swim stres

58 e modulated by the endogenous neurosteroids, allopregnanolone and tetrahydro-deoxycorticosterone.

59 ride, indicating a causal connection between allopregnanolone and the endogenous opioid mechanism.

60 uency and amplitude of sIPSCs, the action of allopregnanolone and the hypertrophy of oxytocin neurone

61 While the mechanism of action of allopregnanolone and the physiological and pharmacologic

62 d ent-pregnanolone, allopregnanolone and ent-allopregnanolone) and show that the ability to potentiat

63 one, a progesterone metabolite also known as allopregnanolone, and 5alpha-androstane-3alpha,17beta-di

64 ositive allosteric modulators clonazepam and allopregnanolone, and by the NMDA receptor antagonists d

65 ); the GABA(A) receptor modulators diazepam, allopregnanolone, and Ro15-4513; and the L-type Ca2+ cha

66 ated that the progesterone (PROG) metabolite allopregnanolone (AP) is more potent than PROG in the tr

67 Endogenous neurosteroids, such as allopregnanolone (AP), regulate neuronal excitability by

68 Neurosteroids, such as allopregnanolone (AP; 3alpha-hydroxy-5alpha-pregnan-20-o

69 Our previous analyses showed that allopregnanolone (APalpha) significantly increased proli

70 Decreased production of allopregnanolone apparently contributes to the pathology

71 IPSCs but enhanced the effect of subsequent allopregnanolone application.

72 of GABA(A) receptor signaling, and identify allopregnanolone as a candidate therapeutic lead.

73 The therapeutic potential of allopregnanolone as a neurogenic molecule is discussed.

74 that a single injection of the neurosteroid allopregnanolone at postnatal day 7 significantly prolon

75 The addition of allopregnanolone, at levels comparable with those found

76 Allopregnanolone attenuated ACTH responses to IL-1beta (

77 increased in pregnant mice in the absence of allopregnanolone attributable to brain region-specific d

78 a clinical neurosteroid general anesthetic, allopregnanolone, believed to occupy the colchicine site

79 Furthermore, blockade of allopregnanolone biosynthesis by preadministration of fi

80 oprogesterone (5alpha-DHP), the last step in allopregnanolone biosynthesis, is catalyzed by 3alpha-hy

81 ion of allopregnanolone reduces anxiety, and allopregnanolone blockade impairs social and affective f

82 conversion of 5alpha-dihydroprogesterone to allopregnanolone by human 3alpha-HSD type III 10- to 30-

83 For catalyzing the oxidation of allopregnanolone by NAD+ the Hill coefficient of the mut

84 so have membrane actions, and in particular, allopregnanolone can act at GABAA receptors to potentiat

85 ty of GABA(A) receptors of epileptic DGCs to allopregnanolone can increase susceptibility to seizures

86 These findings show that allopregnanolone can modulate hippocampal development an

87 Accordingly, allopregnanolone caused an increase in the slow decay ti

88 e more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice.

89 and certain other small molecules increased allopregnanolone concentrations in vivo by activating 3a

90 siological and pharmacological modulation of allopregnanolone concentrations in vivo have been extens

91 the mechanism by which fluoxetine increases allopregnanolone concentrations.

92 Neonatal administration of allopregnanolone delays the onset of neurological sympto

93 The allopregnanolone effect on IPSCs was inhibited by a G-pr

94 Allopregnanolone enhanced GABA-evoked currents less pote

95 The steroids (allopregnanolone, epiallopregnanolone, pregnenolone, tes

96 teroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) facilitates GABA(A) receptor-mediated

97 ther support for the potential usefulness of allopregnanolone for treating NPC disease.

98 racterize the role of 3alpha-HSD type III in allopregnanolone formation and suggest that activation o

99 es to activate 3alpha-HSD type III catalyzed allopregnanolone formation.

100 f the kinetics of human 3alpha-HSD catalyzed allopregnanolone formation.

101 ing baseline noise in DGCs were sensitive to allopregnanolone, furosemide, and loreclezole and insens

102 Allopregnanolone had modest effects on neuron survival t

103 Allopregnanolone had no effect on [Ca2+]i or on the rele

104 s of progesterone and its natural metabolite allopregnanolone have been synthesized and screened usin

105 However, the neural mechanism whereby allopregnanolone improves mood and reduces anxiety is un

106 Here we describe the use of allopregnanolone in 2 pediatric patients with super-refr

107 bitors (SSRIs) could alter concentrations of allopregnanolone in human cerebral spinal fluid and in r

108 The effects of allopregnanolone in MPTP-lesioned mice were more apparen

109 metabolites pregnenolone sulfate (PregS) and allopregnanolone in serum are inversely associated with

110 progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric di

111 ypothesis, the current data demonstrate that allopregnanolone, in a dose-dependent manner, induces a

112 s derivatives 5alpha-dihydroprogesterone and allopregnanolone, in the prefrontal cortex (PFC) of D1CT

113 utic potential of a neurogenic neurosteroid, allopregnanolone, in the restoration of the components o

114 During the appraisal condition, allopregnanolone increased activity in the dorsal medial

115 CR and Western blot validation revealed that allopregnanolone increased the expression of genes that

116 Indeed, allopregnanolone induced opioid inhibition over HPA resp

117 om the isolated supraoptic nucleus, but only allopregnanolone induced significant release of vasopres

118 We hypothesized that allopregnanolone-induced neurite regression was a prelud

119 Surprisingly, in these very young rats, allopregnanolone-induced oxytocin release was inhibited

120 ntrast, in supraoptic nuclei from adult rats allopregnanolone-induced oxytocin release was much small

121 Allopregnanolone-induced proliferation was antagonized b

122 Allopregnanolone-induced proliferation was isomer and st

123 nifedipine, consistent with the finding that allopregnanolone induces a rapid increase in intracellul

124 Thus, in pregnancy, allopregnanolone induces opioid inhibition over HPA axis

125 that the neuroactive progesterone metabolite allopregnanolone induces these changes in HPA responsive

126 egnanolone and epiallopregnanolone following allopregnanolone injection (8 mg/kg, sc).

127 Allopregnanolone is a neuroactive steroid that, like eth

128 Allopregnanolone is a neurosteroid which exhibits anxiol

129 Allopregnanolone is a positive allosteric modulator of G

130 The neurosteroid allopregnanolone is a potent allosteric modulator of the

131 Allopregnanolone is an endogenous steroid, that positive

132 Allopregnanolone is synthesized from progesterone by red

133 -hydroxypregnan-20-one (3alpha,5alpha-THP or allopregnanolone) is a positive modulator of GABAA recep

134 eroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) is a potent endogenous modulator of GA

135 n non-classical progesterone actions through allopregnanolone, its neuroactive steroid metabolite, an

136 Stabilization of allopregnanolone levels from the follicular to the lutea

137 e, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD fro

138 Allopregnanolone levels, but not progesterone levels, we

139 was highly correlated with increased plasma allopregnanolone levels.

140 s provide initial neuroimaging evidence that allopregnanolone may be a target for pharmacologic inter

141 Neuroactive steroids such as allopregnanolone may be potential therapeutic targets fo

142 Furthermore, allopregnanolone may enhance activity in regions linked

143 ted by 5alpha-reductase, and by reduction to allopregnanolone, mediated by 3alpha-hydroxysteroid dehy

144 ntly, the acute addition of the neurosteroid allopregnanolone mitigated functional impairments observ

145 rosterone sulfate (DHEAS), pregnanolone, and allopregnanolone, modulate ionotropic amino acid neurotr

146 , larger in amplitude, and less sensitive to allopregnanolone modulation than those recorded from DGC

147 There was no effect of allopregnanolone on the asphyxia induced impairment of t

148 d subcutaneously (0.2 ml) with either 3mg/kg allopregnanolone or 20% w/v beta-cyclodextrin vehicle.

149 ssant, imipramine, was without any effect on allopregnanolone or androstanediol production.

150 ne) and show that the ability to potentiate (allopregnanolone) or inhibit (pregnanolone) the rho1 rec

151 r association to the change in estradiol and allopregnanolone over the course of pregnancy, suggestin

152 ibition studies for 5alpha-DHP reduction and allopregnanolone oxidation indicated that 3alpha-HSD typ

153 The neurosteroid allopregnanolone partially mediates the anesthetic activ

154 Allopregnanolone partially prevented the decrease in lon

155 anol on hippocampal neurophysiology and that allopregnanolone plays a key role in producing ethanol-i

156 -3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone)-positive cells in the VTA, but did not

157 lone), and 5alpha-pregnane-3alpha-ol-20-one (allopregnanolone) potentiated the GABA-evoked currents f

158 This study examined the effects of allopregnanolone, progesterone and 17beta-oestradiol on

159 These data demonstrate that allopregnanolone promotes the restoration of tyrosine hy

160 e HRSA correlated negatively with changes in allopregnanolone (r(22)=-0.43, p=0.036) and pregNANolone

161 Conversely, allopregnanolone reduced HPA responses in virgin rats.

162 trate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated

163 Exogenous administration of allopregnanolone reduces anxiety, and allopregnanolone b

164 ABA site are potentiated by the neurosteroid allopregnanolone regardless of whether the steroid inter

165 ggerating allosteric actions of zolpidem and allopregnanolone, respectively.

166 ute treatment (once/week for two weeks) with allopregnanolone restored the number of tyrosine hydroxy

167 from pregnant mice compared with virgin, but allopregnanolone reverted the threshold for inducing epi

168 Diazepam, allopregnanolone, Ro15-4513, and nitrendipine had no eff

169 To investigate the brain basis of allopregnanolone's impact on emotion regulation, partici

170 ed sensitivity to Zn2+ indicate that loss of allopregnanolone sensitivity is likely to be due to alte

171 determine whether selection has also altered allopregnanolone sensitivity.

172 These data demonstrate that allopregnanolone significantly increased rat NPC and hNS

173 ahydroisoxazolo[5,4-c]pyridin-3(2H)-one, and allopregnanolone similar to group-housed mice.

174 rodeoxycorticosterone, pregnanolone sulfate, allopregnanolone sulfate, and beta-estradiol) and probed

175 ress may exacerbate TS symptoms by promoting allopregnanolone synthesis in the PFC, and corroborate p

176 nhibitor of the main rate-limiting enzyme in allopregnanolone synthesis.

177 5alpha-reductase, a key enzyme required for allopregnanolone synthesis.

178 regnancy, inhibition of 5alpha-reductase (an allopregnanolone-synthesizing enzyme) with finasteride r

179 In late pregnancy, activity of the allopregnanolone-synthesizing enzymes (5alpha-reductase

180 rtle was probably mediated by its metabolite allopregnanolone [tetrahydroprogesterone (THP)], because

181 e, converting 3alpha-tetrahydroprogesterone (allopregnanolone) to dihydroprogesterone and 3alpha-andr

182 reated mutant mice, but was mostly absent in allopregnanolone-treated animals.

183 In control birth pups, maternal allopregnanolone treatment caused significant changes in

184 Furthermore, in virgin rats, allopregnanolone treatment increased, whereas in pregnan

185 aken together, our results clearly show that allopregnanolone treatment not only reduces cholesterol

186 Here, we further characterized the effect of allopregnanolone treatment on cholesterol accumulation,

187 Furthermore, allopregnanolone treatment significantly enhanced myelin

188 Both changes were significantly reduced by allopregnanolone treatment.

189 lity that are restored by the high levels of allopregnanolone under normal conditions but under patho

190 endogenous oxytocin, and (ii) the effect of allopregnanolone upon oxytocin release changes with age,

191 This is the first report of allopregnanolone use to treat status epilepticus in chil

192 the adult, oxytocin effects are modulated by allopregnanolone via an interaction with inhibitory GABA

193 inactive mutant, increased significantly as allopregnanolone was added to culture media.

194 s also noted that MPTP treated mice to which allopregnanolone was administered had an increase in Brd

195 Sensitivity to allopregnanolone was also measured in FAST and SLOW mice

196 Compared with placebo, allopregnanolone was associated with reduced activity in

197 tivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant in

198 Mean serum allopregnanolone was lower in AN and OW/OB than HC (AN 9

199 5alpha-reduced neurosteroids, predominantly allopregnanolone, we found that immunostaining in the CA

200 anesthetic steroids such as alphaxalone and allopregnanolone, which have a 5alpha-configuration at t

201 amide, chlorthalidone, and the neurosteroid, allopregnanolone, which inhibits chloride transport, pro

202 s of the weight spectrum have low mean serum allopregnanolone, which is associated with increased dep

203 Cs is significantly longer in the absence of allopregnanolone, which now has no significant effect.