Structure-Dependent Activity of Natural GABA(A) Receptor Modulators
Abstract
:1. Introduction
2. Method
3. Natural GABA(A) Receptor Modulators
3.1. Alkaloids
3.2. Alkanes
3.3. Phenols
3.3.1. Flavones
- Hydroxylation in position 5 and 7 or in position 6 leads to increased receptor affinity.
- Methoxylation in position 6 or 8 also raises affinity of the compounds, even more when occurring in both positions.
- The affinity furthermore increases by hydroxylation in position 2’, while methoxylation in the same position leads to a loss of affinity.
3.3.2. Flavanes
3.3.3. Isoflavonoids and Chalcones
3.3.4. Phenylpropanes, Kavalactones and Lignans
3.3.5. Coumarins
3.3.6. Diarylheptanoids, Stilbenes and Phenanthrenes
3.3.7. Simple Phenols and Polyphenols
3.4. Terpenes
3.4.1. Monoterpenes
3.4.2. Sesquiterpenes
3.4.3. Diterpenes
3.4.4. Triterpenes
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 228–231 are available from the author. |
Cmpd | Source | Assay | Subtype | c(GABA) | Imax [%] | c [µM] | IC50 [µM] | Ref. |
---|---|---|---|---|---|---|---|---|
1 | Colchicum autumnale | Xenopus oocytes | α1β2γ2L | 10 µM | 59.9 ± 6.2 | 100 | [23] | |
19 | Aconitum leucostomum | Hippocampal neurons | 19.6 | [31] | ||||
22 | Oenanthe fistulosa | HEK-293T cells | α1β2γ2L | 1.39 | [35] | |||
23 | Oenanthe fistulosa | HEK-293T cells | α1β2γ2L | 0.835 | [35] | |||
26 | Cicuta virosa | Hippocampal neurons | 10 µM | 90 | 10 | 0.96 | [37] | |
34 | Xenopus oocytes | α1β2γ2S | 14.8 ± 0.8 | 30 | [54] | |||
45 | Xenopus oocytes | α1β2γ2S | 12.1 ± 0.5 | 30 | [54] | |||
56 | Scuttelaria baicalensis | CA1 neurons | 10 µM | 38.2 ± 6 | 100 | [46] | ||
63 | Xenopus oocytes | α1β2γ2S | 50.6 ± 0.8 | 30 | [54] | |||
63 | Matricaria recutita | Cerebellar granule cells | 10 µM | 32 ± 4 | 10 | [55] | ||
63 | Xenopus oocytes | α1β2γ2L | 40 µM | 49.6 | 100 | 8 | [56] | |
63 | Xenopus oocytes | α1β2γ2S | 6.9 ± 0.3 | [57] | ||||
64 | HEK-293T cells | α1β2γ2 | 66.5 ± 6.8 | 6.62 ± 2.11 | [62] | |||
73 | Xenopus oocytes | α1β2γ2S | 84.5 ± 4.9 | 30 | [54] | |||
74 | Xenopus oocytes | α1β2γ2S | 38.4 ± 4.8 | 30 | [54] | |||
84 | Xenopus oocytes | α1β2γ2L | 40/20 µM | 90.6/97 | 100 | 14.7/8.7 | [56] | |
96 | Xenopus oocytes | α1β2γ2L | 40/5 µM | 51/40 | 100 | 29.2/11.7 | [56] | |
134 | Xenopus oocytes | α1β2γ2L | 5.79 | [108] | ||||
154 | Dorsal root ganglia | 300 µM | 100 | 30 | 21 | [117] | ||
154 | HEK-293T cells | α1β2δ | 60 | 300 | [118] | |||
197 | Illicium anisatum | Dorsal root ganglia | 30 µM | 41.7 | 1 | 1.10 ± 1.40 | [144] | |
209 | Ginkgo biloba | Xenopus oocytes | α1β2γ2L | 300 µM | 11.9 ± 1.7 | [152] | ||
210 | Ginkgo biloba | Xenopus oocytes | α1β2γ2L | 300 µM | 10.1 ± 2.9 | [152] | ||
210 | Ginkgo biloba | Cortical neurons | α1β2γ2L | 30 µM | 63.2 ± 0.3 | 50 | 73 | [153] |
211 | Ginkgo biloba | Xenopus oocytes | α1β2γ2L | 300 µM | 12.0 ± 2.2 | [152] | ||
212 | Ginkgo biloba | Cortical neurons | α1β2γ2L | 30 µM | 46.8 ± 0.3 | 50 | 76 µM | [153] |
Cmpd | Source | Assay | Subtype | c(GABA) | Pmax [%] | c [µM] | EC50 [µM] | Ref. |
---|---|---|---|---|---|---|---|---|
5 | Piper nigrum | Xenopus oocytes | α1β2γ2S | EC5–10 | 302 ± 26 | 300 | 52 ± 9 | [25] |
6 | Piper nigrum | Xenopus oocytes | α1β2γ2S | EC5–10 | 187 ± 10 | 300 | 56 ± 19 | [25] |
20 | Xenopus oocytes | α1β2γ2 | 1 µM | 295 ± 50 | 300 | [33] | ||
31–33 | Cussonia zimmermannii | Xenopus oocytes | α1β2γ2 | 110–440 | 0.6–3.5 | [40] | ||
46 | Scuttelaria baicalensis | Xenopus oocytes | α1β2γ2 | EC1 | 57 ± 6 | 30 | 3 | [48] |
66 | Xenopus oocytes | α1β2γ2 | EC2–5 | 47 ± 5 | 10 | [57] | ||
82 | Xenopus oocytes | α4β4δ | 68 ± 5 | 100 | [76] | |||
88 | Sophora flavescens | Xenopus oocytes | α1β2γ2S | EC3–10 | 578.5 ± 68.8 | 8.1 ± 1.4 | [79] | |
89 | Sophora flavescens | Xenopus oocytes | α1β2γ2S | EC3–10 | 267.6 ± 56.6 | 5.0 ± 2.3 | [79] | |
90 | Sophora flavescens | Xenopus oocytes | α1β2γ2S | EC3–10 | 604.9 ± 108.2 | 15.0 ± 3.6 | [79] | |
92 | Morus alba | Xenopus oocytes | α1β2γ2S | 730.4 ± 76.7 | 100 | 13.8 ± 1.5 | [81] | |
93 | Morus alba | Xenopus oocytes | α1β2γ2S | 715.8 ± 56.1 | 100 | 16.7 ± 2.0 | [81] | |
94 | Morus alba | Xenopus oocytes | α1β2γ2S | 719.3 ± 63.3 | 100 | 13.4 ± 1.6 | [81] | |
95 | Adenocarpus cinncinatus | Xenopus oocytes | α1β2γ2S | EC5–10 | 552.73 ± 84.07 | 500 | 2.8 ± 1.4 | [82] |
97 | Glycyrrhiza glabra | Dorsal raphe neurons | α2β2/3γ2L | 2 µM | 581 ± 91 | 3 | [83] | |
98 | Dorsal raphe neurons | EC10 | 151 | 10 | [84] | |||
99 | Sophora flavescens | Xenopus oocytes | α1β2γ2S | EC3–10 | 891.5 ± 163.0 | 4.0 ± 2.4 | [79] | |
101 | HEK-293T cells | α1β2γ2 | 290 ± 28 | [86] | ||||
102 | Acorus calamus | Xenopus oocytes | α1β2γ2S | EC5–10 | 1200 ± 163 | 500 | 171.5 ± 34.6 | [87] |
103 | Magnolia officinalis | Xenopus oocytes | α1β2γ2S | 1315 ± 281 | 300 | 36.2 ± 14.7 | [88] | |
106 | HEK-293T cells | 10.1 ± 10.5 | [93] | |||||
107 | HEK-293T cells | 16.9 ± 0.3 | [93] | |||||
108 | HEK-293T cells | 10.5 ± 2.3 | [93] | |||||
109 | Cortical neurons | 10 µM | 158 ± 20 | 1 | 0.04258 | [94] | ||
110 | Piper methysticum | Neonatal rat gastric-brainstem preparation | 31.5 ± 3.9 | 300 | 93 | [95] | ||
111 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 218.1 ± 20.8 | 21.8 ± 7.5 | [96] | |
112 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 245.0 ± 59.6 | 52.2 ± 24.8 | [96] | |
113 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 885.8 ± 291.2 | 135.6 ± 85.7 | [96] | |
114 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 168.7 ± 41.5 | 36.6 ± 16.4 | [96] | |
115 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 129.7 ± 36.8 | 118.7 ± 54.4 | [96] | |
116 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 395.6 ± 27.2 | 31.5 ± 7.1 | [96] | |
117 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 288.8 ± 23.7 | 12.8 ± 3.1 | [96] | |
118 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 793.4 ± 107.4 | 79.2 ± 19.4 | [96] | |
119 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 362.5 ± 87.1 | 54.6 ± 28.8 | [96] | |
121 | Cnidium monnieri | Xenopus oocytes | α1β2γ2S | 54 ± 13 | [99] | |||
121 | Angelica pubescens | Xenopus oocytes | α1β2γ2S | EC5–10 | 25.8 ± 12.7 | 300 | [100] | |
122 | Xenopus oocytes | α1β2γ2S | 57 ± 4 | [99] | ||||
124 | Xenopus oocytes | α1β2γ2S | 550 ± 71 | 100 | 25 ± 8 | [99] | ||
125 | Xenopus oocytes | α1β2γ2S | 34 ± 6 | [99] | ||||
126 | Angelica pubescens | Xenopus oocytes | α1β2γ2S | EC5–10 | 204.5 ± 33.2 | 300 | [89] | |
127 | Cnidium monnieri | Xenopus oocytes | α1β2γ2S | 124 ± 11 | 100 | 14 ± 1 | [99] | |
127 | Angelica pubescens | Xenopus oocytes | α1β2γ2S | EC5–10 | 273.6 ± 39.4 | 300 | [100] | |
128 | Angelica pubescens | Xenopus oocytes | α1β2γ2S | EC5–10 | 61.2 ± 20.2 | 300 | [100] | |
129 | Angelica pubescens | Xenopus oocytes | α1β2γ2S | EC5–10 | 38.0 ± 21.3 | 300 | [100] | |
131 | Haloxylon scoparium | Xenopus oocytes | α1β2γ2S | 144.6 ± 35.3 | 500 | 140.2 ± 51.2 | [106] | |
132 | Rhizoma curcumae oil | HEK-293T cells | α1β2γ2 | 1 µM | 120 ± 6 | 50 | [107] | |
133 | Xenopus oocytes | α1β2γ2L | EC10 (3 µM) | 126 ± 15 | 100 | 58.24 | [108] | |
135 | Pholidota chinensis | Xenopus oocytes | α1β2γ2S | EC3–10 | 786.8 ± 72.1 | 300 | 175.5 ± 25.5 | [109] |
136 | Pholidota chinensis | Xenopus oocytes | α1β2γ2S | EC3–10 | 1512.9 ± 176.5 | 300 | 52.5 ± 17.0 | [109] |
137 | Adenocarpus cinncinatus | Xenopus oocytes | α1β2γ2S | EC5–10 | 771.09 ± 57.94 | 500 | 40.7 ± 4.08 | [82] |
138 | Adenocarpus cinncinatus | Xenopus oocytes | α1β2γ2S | EC5–10 | 640.02 ± 53.56 | 500 | 8.6 ± 1.6 | [82] |
139 | Adenocarpus cinncinatus | Xenopus oocytes | α1β2γ2S | EC5–10 | 490.97 ± 22.34 | 500 | 18.8 ± 2.3 | [82] |
140 | Juncus effusus | Xenopus oocytes | α1β2γ2S | EC5–10 | 188 ± 20 | 300 | 31 ± 8 | [110] |
141 | Juncus effusus | Xenopus oocytes | α1β2γ2S | EC5–10 | 239 ± 18 | 300 | 27 ± 6 | [110] |
149 | Xenopus oocytes | α1β2γ2L | EC5–14 | 1251 ± 73 | 300 | 247.7 | [115] | |
150 | Xenopus oocytes | α1β2γ2L | EC15–24 | 1106 ± 73 | 300 | 236.9 | [115] | |
151 | Xenopus oocytes | α1β2γ2L | EC25–39 | 571 ± 123 | 300 | 111.2 | [115] | |
152 | Xenopus oocytes | α1β2γ2L | EC15–24 | 968 ± 88 | 300 | 190.5 | [115] | |
153 | Xenopus oocytes | α1β2γ2L | EC15–24 | 377 ± 156 | 300 | 469.1 | [115] | |
160 | Xenopus oocytes | α1β3γ2S | EC20 | 416 ± 72 | 100 | [123] | ||
161 | Xenopus oocytes | α1β2γ2 | 1 µM | 224 ± 85 | 300 | [33] | ||
162 | Xenopus oocytes | α1β2γ2 | 1 µM | 453 ± 176 | 300 | [33] | ||
163 | Xenopus oocytes | α1β2γ2 | 1 µM | 340 ± 70 | 300 | [33] | ||
164 | Xenopus oocytes | α1β2γ2 | 1 µM | 213 ± 105 | 300 | [33] | ||
165 | Xenopus oocytes | α1β2γ2 | 1 µM | 477 ± 68 | 300 | [33] | ||
166 | Xenopus oocytes | α1β2γ2 | 1 µM | 809 ± 118 | 300 | [33] | ||
167 | HEK-293T cells | α1β2γ2 | 1 µM | 156 ± 26 | 1000 | [33] | ||
168 | HEK-293T cells | α1β2γ2 | 1 µM | 168 ± 42 | 1000 | [33] | ||
169 | HEK-293T cells | α1β2γ2 | 1 µM | 116 ± 56 | 1000 | [33] | ||
170 | HEK-293T cells | α1β2γ2 | 1 µM | 179 ± 55 | 1000 | [33] | ||
171 | Xenopus oocytes | α1β2γ2 | 1 µM | 737 ± 234 | 300 | [33] | ||
175 | Xenopus oocytes | α1β2γ2S | EC20 | 496 ± 113 | 100 | [131] | ||
175 | Xenopus oocytes | α1β2γ2S | EC20 | 96.2 ± 3.8 | 50 | [132] | ||
176 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 834.6 ± 77.5 | 70.6 ± 12.2 | [96] | |
177 | HEK-293T cells | α1β2γ2 | 1 µM | 117 ± 57 | 1000 | [33] | ||
178 | HEK-293T cells | α1β2γ2 | 1 µM | 115 ± 52 | 1000 | [33] | ||
179 | Rhizoma curcumae oil | HEK-293T cells | α1β2γ2 | 1 µM | 133 ± 10 | 50 | [107] | |
180 | Rhizoma curcumae oil | HEK-293T cells | α1β2γ2 | 1 µM | 251 ± 16 | 300 | 34.4 ± 2.9 | [107] |
182 | Valeriana officinalis | Xenopus oocytes | α1β2γ2S | EC5–10 | 400.0 ± 77.6 | 100 | 13.6 ± 4.1 | [135] |
183 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 383.5 ± 89.3 | 57.3 ± 19.7 | [96] | |
184 | Kadsura longipedunculata | Xenopus oocytes | α1β2γ2S | EC5–10 | 413.4 ± 66.3 | 118.4 ± 29.9 | [96] | |
188 | Acorus calamus | Xenopus oocytes | α1β2γ2S | EC5–10 | 241 ± 23.1 | 500 | 34.0 ± 6.7 | [87] |
189 | Acorus calamus | Xenopus oocytes | α1β2γ2S | EC5–10 | 669 ± 112 | 1000 | 64.8 ± 19.8 | [87] |
190 | Acorus calamus | Xenopus oocytes | α1β2γ2S | EC5–10 | 164 ± 42.9 | 500 | 109.4 ± 46.6 | [87] |
191 | Acorus calamus | Xenopus oocytes | α1β2γ2S | EC5–10 | 886 ± 105 | 1000 | 135.1 ± 34.4 | [87] |
192 | Acorus calamus | Xenopus oocytes | α1β2γ2S | EC5–10 | 588 ± 126 | 300 | 65.3 ± 21.6 | [87] |
193 | Aristolochia manshuriensis | Xenopus oocytes | α1β2γ2S | EC5–10 | 70.7 ± 2.6 | 1000 | 56.02 ± 5.09 | [140] |
194 | Atractylodes macrocephala | Xenopus oocytes | α1β2γ2S | EC1–10 | 96 ± 3 | 300 | 12 ± 1 | [141] |
195 | Atractylodes macrocephala | Xenopus oocytes | α1β2γ2S | EC1–10 | 166 ± 122 | 300 | 70 ± 17 | [141] |
196 | Atractylodes macrocephala | Xenopus oocytes | α1β2γ2S | EC1–10 | 157 ± 12 | 300 | 99 ± 20 | [141] |
198 | Acremonium strictum | Xenopus oocytes | α1β1γ2S | EC20 | 180 | 1 | 0.05 ± 0.02 | [145] |
202 | Boswellia serrata | Xenopus oocytes | α1β2γ2S | EC5–10 | 397.5 ± 34.0 | 100 | 8.7 ± 1.3 | [148] |
203 | Platycladus orientalis | Xenopus oocytes | α1β2γ2S | EC5–10 | 425.2 ± 96.5 | 500 | 141.6 ± 68.0 | [149] |
204 | Platycladus orientalis | Xenopus oocytes | α1β2γ2S | EC5–10 | 855.7 ± 114.9 | 500 | 33.2 ± 8.7 | [149] |
207 | Curcuma kwangsiensis | Xenopus oocytes | α1β2γ2S | EC3–10 | 309.4 ± 35.6 | 300 | 24.9 ± 8.8 | [151] |
208 | Curcuma kwangsiensis | Xenopus oocytes | α1β2γ2S | EC3–10 | 211.0 ± 26.0 | 300 | 35.7 ± 8.8 | [151] |
220 | Panax ginseng | Xenopus oocytes | α1β2γ2S | 10 µM | 53.2 ± 12.3 | [162] | ||
221 | Panax ginseng | Xenopus oocytes | α1β2γ2S | 10 µM | 23.3 ± 1.4 | 100 | 23.1 ± 8.6 | [163] |
222 | Panaxginseng | Xenopus oocytes | α1β2γ2S | 10 µM | 54.1 ± 1.7 | 100 | 17.1 ± 2.2 | [163] |
228 | Actaea racemosa | Xenopus oocytes | α1β2γ2S | EC3–10 | 378 ± 64 | 300 | 36 ± 14 | [167] |
229 | Actaea racemosa | Xenopus oocytes | α1β2γ2S | EC3–10 | 256 ± 40 | 300 | 28 ± 17 | [167] |
230 | Actaea racemosa | Xenopus oocytes | α1β2γ2S | EC3–10 | 289 ± 45 | 300 | 26 ± 7 | [167] |
231 | Actaea racemosa | Xenopus oocytes | α1β2γ2S | EC3–10 | 1947 ± 185 | 300 | 27 ± 8 | [167] |
Cmpd | Source | Binding Site | Ligand | IC50 [µM] | Ki [µM] | Stimulation [%] | c [µM] | Ref. |
---|---|---|---|---|---|---|---|---|
4 | Leonurus japonicus | GABA/muscimol | [3H]gabazine | 15,000 | [24] | |||
19 | Aconitum leucostomum | GABA/muscimol | [3H]muscimol | 7.06 | [31] | |||
218 | GABA/muscimol | [3H]GABA | 64 ± 5 | [160] | ||||
2 | Colchicum szovitsii | benzodiazepine | [3H]flunitrazepam | 25% of 10 µM allopregnanolone | 10 | [22] | ||
3 | Colchicum szovitsii | benzodiazepine | [3H]flunitrazepam | 25% of 10 µM allopregnanolone | 10 | [22] | ||
4 | Leonurus japonicus | benzodiazepine | [3H]flumazenil | 123,000 | [24] | |||
16 | Oceanapia sp. | benzodiazepine | [3H]diazepam | 39 | 25 | [30] | ||
17 | Oceanapia sp. | benzodiazepine | [3H]diazepam | 32 | 25 | [30] | ||
18 | Oceanapia sp. | benzodiazepine | [3H]diazepam | 30 | 25 | [30] | ||
34 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 7.81 ± 1.81 | [42] | |||
35 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 4.20 ± 0.27 | [42] | |||
36 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.21 ± 0.10 | [42] | |||
37 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.56 ± 0.07 | [42] | |||
38 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.027 ± 0.003 | [42] | |||
39 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 6.42 ± 0.95 | [41] | |||
40 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.0075 ± 0.004 | [42] | |||
41 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.28 ± 0.076 | [41] | |||
42 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 2.64 ± 0.36 | [42] | |||
43 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.034 ± 0.001 | [42] | |||
44 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 9.46 ± 1.45 | [42] | |||
45 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.69 ± 0.12 | 0.64 ± 0.26 | [41,42] | ||
46 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 1.26 ± 0.24 | 1.52 ± 0.13 | [41,42] | ||
47 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.36 ± 0.095 | 0.20 ± 0.05 | [41,42] | ||
48 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.008 ± 0.0002 | 0.0061 ± 0.0001 | [41,42] | ||
49 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.31 ± 0.088 | [41] | |||
50 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.0038 ± 0.005 | [42] | |||
51 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 5.58 ± 0.02 | [42] | |||
52 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 21.0 ± 1.79 | [41] | |||
53 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 21.4 ± 1.42 | [41] | |||
54 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 10.1 ± 1.68 | [41] | |||
55 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | >100 | [41] | |||
56 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 0.14 ± 0.01 | 0.89 ± 0.06 | [41,42] | ||
57 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 22.6 ± 1.30 | [41] | |||
58 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 12.5 ± 1.58 | [41] | |||
59 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 1.27 ± 0.08 | [41] | |||
60 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 6.80 ± 1.18 | [41] | |||
61 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 32.8 ± 1.51 | [41] | |||
62 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 45.7 ± 2.48 | [41] | |||
63 | Tanacetum parthenium | benzodiazepine | [3H]flumazenil | 12 | 9 | [60] | ||
63 | Salvia officinalis | benzodiazepine | [3H]flumazenil | 30 ± 4 | [65] | |||
63 | Rhus pyroides | benzodiazepine | [3H]flumazenil | 10.0 ± 1.18 | [59] | |||
63 | Matricaria recutita | benzodiazepine | [3H]flunitrazepam | 4 | [58] | |||
66 | Artemisia herba-alba | benzodiazepine | [3H]flumazenil | 8 | [66] | |||
66 | Salvia officinalis | benzodiazepine | [3H]flumazenil | 1.3 ± 0.2 | [65] | |||
67 | Salvia officinalis | benzodiazepine | [3H]flumazenil | 350 ± 37 | [65] | |||
68 | Salvia coerulea | benzodiazepine | [3H]flunitrazepam | 200 | [67] | |||
68 | Salvia coerulea | benzodiazepine | [3H]zolpidem | 20 | [67] | |||
69 | Artemisia herba-alba | benzodiazepine | [3H]flumazenil | 100 | [66] | |||
70 | Artemisia herba-alba | benzodiazepine | [methyl-3H]DZP | 1.3 | [68] | |||
71 | Artemisia herba-alba | benzodiazepine | [methyl-3H]DZP | 22.7 | [68] | |||
78 | Hypericum perforatum | benzodiazepine | [3H]flunitrazepam | 0.0149 | [74] | |||
78 | Searsia pyroides | benzodiazepine | [3H]flunitrazepam | 37 | [59] | |||
79 | Searsia pyroides | benzodiazepine | [3H]flunitrazepam | 28 | [59] | |||
85 | Mentha aquatica | benzodiazepine | [3H]flumazenil | 2600 | [78] | |||
87 | Scuttelaria baicalensis | benzodiazepine | [3H]flunitrazepam | 21.4 ± 1.32 | [41] | |||
91 | Glycyrrhiza glabra | benzodiazepine | [3H]flumazenil | 1.63 | [80] | |||
98 | benzodiazepine | [3H]flunitrazepam | 0.453 | [84] | ||||
121 | Angelica dahurica | benzodiazepine | [3H]diazepam | 8.0 ± 0.8 | [98] | |||
122 | Angelica dahurica | benzodiazepine | [3H]diazepam | 0.36 ± 0.03 | [98] | |||
123 | Angelica dahurica | benzodiazepine | [3H]diazepam | 12 ± 3 | [98] | |||
154 | benzodiazepine | [3H]flunitrazepam | 74.44 | [120] | ||||
156 | benzodiazepine | [3H]flunitrazepam | 15.69 | [120] | ||||
157 | benzodiazepine | [3H]flunitrazepam | 90.02 | [120] | ||||
160 | benzodiazepine | [3H]flunitrazepam | 130.9 | [124] | ||||
181 | Cyperus rotundus | benzodiazepine | [3H]flunitrazepam | 105.0 ± 1.60 | [134] | |||
186 | Mentha aquatica | benzodiazepine | [3H]flumazenil | 190,000 | [78] | |||
199 | Salvia miltiorrhiza | benzodiazepine | [3H]flunitrazepam | 0.3 | [146] | |||
200 | Salvia officinalis | benzodiazepine | [3H]flumazenil | 7.2 ± 0.7 | [65] | |||
201 | Salvia officinalis | benzodiazepine | [3H]flumazenil | 0.8 ± 0.1 | [65] | |||
205 | Aloysia virgata | benzodiazepine | [3H]flumazenil | 111 ± 13 | [150] | |||
206 | Aloysia virgata | benzodiazepine | [3H]flumazenil | 56 ± 19 | [150] | |||
2 | Colchicum szovitsii | TBPS/picrotoxin | [35S]TBPS | 25% of 10 µM allopregnanolone | 10 | [22] | ||
3 | Colchicum szovitsii | TBPS/picrotoxin | [35S]TBPS | 25% of 10 µM allopregnanolone | 10 | [22] | ||
7 | Corydalis cava | TBPS/picrotoxin | [3H]bicuculline | 121 ± 2 | 0.1 | [26] | ||
8 | Corydalis cava | TBPS/picrotoxin | [3H]bicuculline | 149 ± 2 | 0.01 | [26] | ||
9 | Corydalis cava | TBPS/picrotoxin | [3H]bicuculline | 130 ± 3 | 0.1 | [26] | ||
10 | Corydalis cava | TBPS/picrotoxin | [3H]bicuculline | 146 ± 7 | 0.01 | [26] | ||
11 | Corydalis cava | TBPS/picrotoxin | [3H]bicuculline | 147 ± 3 | 0.1 | [26] | ||
24 | Cicuta virosa | TBPS/picrotoxin | [3H]EBOB | 0.54 ± 0.03 | [37] | |||
25 | Cicuta virosa | TBPS/picrotoxin | [3H]EBOB | 2.01 ± 0.09 | [37] | |||
26 | Cicuta virosa | TBPS/picrotoxin | [3H]EBOB | 1.15 ± 0.09 | [37] | |||
27 | Cicuta virosa | TBPS/picrotoxin | [3H]EBOB | 6.01 ± 0.29 | [37] | |||
28 | Cicuta virosa | TBPS/picrotoxin | [3H]EBOB | 7.87 ± 0.83 | [37] | |||
65 | Valeriana jatamansi | TBPS/picrotoxin | [35S]TBPS | 0.50 ± 0.17 | [63] | |||
79 | Rhus parviflora | TBPS/picrotoxin | [35S]TBPS | 0.149 | 0.091 | [75] | ||
80 | Rhus parviflora | TBPS/picrotoxin | [35S]TBPS | 0.073 | 0.045 | [75] | ||
81 | Rhus parviflora | TBPS/picrotoxin | [35S]TBPS | 0.455 | 0.280 | [75] | ||
145 | Ecklonia cava | TBPS/picrotoxin | [35S]TBPS | 7.180 | 4.419 | [80] | ||
146 | Ecklonia cava | TBPS/picrotoxin | [35S]TBPS | 1.739 | 1.070 | [80] | ||
147 | Ecklonia cava | TBPS/picrotoxin | [35S]TBPS | 4.991 | 3.072 | [80] | ||
148 | Ecklonia cava | TBPS/picrotoxin | [35S]TBPS | 2.422 | 1.491 | [80] | ||
154 | TBPS/picrotoxin | [35S]TBPS | 13 ± 4 | [117] | ||||
155 | TBPS/picrotoxin | [35S]TBPS | 37 ± 8 | [117] | ||||
197 | Illicium anisatum | TBPS/picrotoxin | [3H]EBOB | 0.43 | [144] | |||
212 | Ginkgo biloba | TBPS/picrotoxin | [35S]TBPS | 39 | [154] |
Cmpd | Anxiety/Stress | Sedation | Convulsions | Myorelaxation | Analgesia | Ref. | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
VC | FP | EPM | OF | HB | LD | MB | FS | TS | SIH | LMA | PIS | EIS | MES | PTZ | PTX | RR | HW | TF | TI | ||
11 | 0.5 | 50 | 50 | [27] | |||||||||||||||||
12 | 5 | [28] | |||||||||||||||||||
13 | 5 | [28] | |||||||||||||||||||
14 | 2.5 | [28] | |||||||||||||||||||
15 | 10 | – | – | – | [29] | ||||||||||||||||
19 | 0.25 | [32] | |||||||||||||||||||
21 | + | + | + | [34] | |||||||||||||||||
45 | 1 | – | 3 | + | – | – | 25 | [50,51,52,53] | |||||||||||||
46 | 7.5 | 7.5 | – | 5 | 5 | – | – | [48,49] | |||||||||||||
54 | 10 | + | + | – | [43,44] | ||||||||||||||||
55 | 10 | [43] | |||||||||||||||||||
56 | – | – | – | – | – | [47] | |||||||||||||||
63 | 0.5 | 50 | 30 | 25 | 0.6 | 25 | – | [55,58,61] | |||||||||||||
65 | 1 | – | [64] | ||||||||||||||||||
68 | 2 | [67] | |||||||||||||||||||
72 | 0.2 | – | [69] | ||||||||||||||||||
73 | 0.5 | [70] | |||||||||||||||||||
75 | 50 | [71] | |||||||||||||||||||
76 | 100 | [72] | |||||||||||||||||||
77 | 2.5 | 5 | 5 | [73] | |||||||||||||||||
80 | 12.5 | [75] | |||||||||||||||||||
84 | 5 | [77] | |||||||||||||||||||
86 | 1 | [64] | |||||||||||||||||||
98 | 25 | [84] | |||||||||||||||||||
103 | 20 | 0.1 | [89,90] | ||||||||||||||||||
105 | 0.05 | [92] | |||||||||||||||||||
107 | 3 | [93] | |||||||||||||||||||
109 | 4 | 4 | [94] | ||||||||||||||||||
120 | 5 | [97] | |||||||||||||||||||
121 | 5 | 5 | 5 | 300 | [102,103] | ||||||||||||||||
125 | 5 | 5 | 5 | [103] | |||||||||||||||||
127 | 259 | [101] | |||||||||||||||||||
130 | 150 | [105] | |||||||||||||||||||
142 | 50 | [111] | |||||||||||||||||||
143 | 300 | 100 | 100 | 100 | [112] | ||||||||||||||||
144 | 2.5 | 2.5 | 5 | [113] | |||||||||||||||||
149 | 5 | 50 | [116] | ||||||||||||||||||
158 | 200 | 300 | 200 | [121] | |||||||||||||||||
159 | 72.75 | [122] | |||||||||||||||||||
163 | 25 | 25 | 25 | 25 | [125] | ||||||||||||||||
171 | [126] | ||||||||||||||||||||
172 | 25 | 25 | 25 | 75 | [127,128] | ||||||||||||||||
173 | 25 | 25 | 25 | 25 | – | [129] | |||||||||||||||
174 | 400 | 100 | 200 | [130] | |||||||||||||||||
180 | 100 | [107] | |||||||||||||||||||
182 | 3 | [137] | |||||||||||||||||||
185 | 10 | [138] | |||||||||||||||||||
187 | + | [139] | |||||||||||||||||||
199 | 10 | – | [146] | ||||||||||||||||||
205 | 0.3 | 1 | [150] | ||||||||||||||||||
206 | 1 | 0.3 | 1 | [150] | |||||||||||||||||
213 | + | [157] | |||||||||||||||||||
214 | 0.5 | – | [156] | ||||||||||||||||||
215 | + | [157] | |||||||||||||||||||
216 | + | [158] | |||||||||||||||||||
217 | 10 | 3 | [159] | ||||||||||||||||||
219 | 30 | [161] | |||||||||||||||||||
223 | 10 | 50 | [164] | ||||||||||||||||||
224 | 10 | [164] | |||||||||||||||||||
225 | 10 | [165] | |||||||||||||||||||
226 | 10 | [165] | |||||||||||||||||||
231 | 0.6 | 6 | 0.2 | 20 | [168] |
© 2018 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Çiçek, S.S. Structure-Dependent Activity of Natural GABA(A) Receptor Modulators. Molecules 2018, 23, 1512. https://doi.org/10.3390/molecules23071512
Çiçek SS. Structure-Dependent Activity of Natural GABA(A) Receptor Modulators. Molecules. 2018; 23(7):1512. https://doi.org/10.3390/molecules23071512
Chicago/Turabian StyleÇiçek, Serhat Sezai. 2018. "Structure-Dependent Activity of Natural GABA(A) Receptor Modulators" Molecules 23, no. 7: 1512. https://doi.org/10.3390/molecules23071512