Abstract
The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384), a cyclic derivative of GABA, were investigated and compared with those of aniracetam in an animal model of amnesia, using a passive avoidance task with animals that have GABAergic neuronal dysfunctions. Pre- and post-training administration of DM-9384 and aniracetam amelioratedbicuculline-induced amnesia, as indicated by parameters such as % retention and step-down latency. DM-9384 ameliorated picrotoxin-induced amnesia when administered pre-training, but not when administered post-training. Aniracetam failed to improve the picrotoxin-induced amnesia. DM-9384 displaced [3H]muscimol binding to GABAA receptors (-log IC50 = 8.07 M; Hill value = 0.23 ± 0.04), but failed to displace about 20% of the specific muscimol binding, whereas aniracetam showed only a weak effect (- log IC50 = 3.63 M; Hill value = 0.37 ± 0.06). From these results, it appears that DM-9384 ameliorated the GABA antagonist-induced amnesia by interacting with some GABAA receptors directly and/or indirectly.
| Original language | English |
|---|---|
| Pages (from-to) | 143-149 |
| Number of pages | 7 |
| Journal | European Journal of Pharmacology |
| Volume | 178 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 20-03-1990 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Pharmacology
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Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions. / Nabeshima, Toshitaka; Yukihiro Noda, Noda; Keiko Tohyama, Tohyama; Jiroh Itoh, Itoh; Tsutomu Kameyama, Kameyama.
In: European Journal of Pharmacology, Vol. 178, No. 2, 20.03.1990, p. 143-149.Research output: Contribution to journal › Article
TY - JOUR
T1 - Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions
AU - Nabeshima, Toshitaka
AU - Yukihiro Noda, Noda
AU - Keiko Tohyama, Tohyama
AU - Jiroh Itoh, Itoh
AU - Tsutomu Kameyama, Kameyama
PY - 1990/3/20
Y1 - 1990/3/20
N2 - The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384), a cyclic derivative of GABA, were investigated and compared with those of aniracetam in an animal model of amnesia, using a passive avoidance task with animals that have GABAergic neuronal dysfunctions. Pre- and post-training administration of DM-9384 and aniracetam amelioratedbicuculline-induced amnesia, as indicated by parameters such as % retention and step-down latency. DM-9384 ameliorated picrotoxin-induced amnesia when administered pre-training, but not when administered post-training. Aniracetam failed to improve the picrotoxin-induced amnesia. DM-9384 displaced [3H]muscimol binding to GABAA receptors (-log IC50 = 8.07 M; Hill value = 0.23 ± 0.04), but failed to displace about 20% of the specific muscimol binding, whereas aniracetam showed only a weak effect (- log IC50 = 3.63 M; Hill value = 0.37 ± 0.06). From these results, it appears that DM-9384 ameliorated the GABA antagonist-induced amnesia by interacting with some GABAA receptors directly and/or indirectly.
AB - The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384), a cyclic derivative of GABA, were investigated and compared with those of aniracetam in an animal model of amnesia, using a passive avoidance task with animals that have GABAergic neuronal dysfunctions. Pre- and post-training administration of DM-9384 and aniracetam amelioratedbicuculline-induced amnesia, as indicated by parameters such as % retention and step-down latency. DM-9384 ameliorated picrotoxin-induced amnesia when administered pre-training, but not when administered post-training. Aniracetam failed to improve the picrotoxin-induced amnesia. DM-9384 displaced [3H]muscimol binding to GABAA receptors (-log IC50 = 8.07 M; Hill value = 0.23 ± 0.04), but failed to displace about 20% of the specific muscimol binding, whereas aniracetam showed only a weak effect (- log IC50 = 3.63 M; Hill value = 0.37 ± 0.06). From these results, it appears that DM-9384 ameliorated the GABA antagonist-induced amnesia by interacting with some GABAA receptors directly and/or indirectly.
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U2 - 10.1016/0014-2999(90)90469-M
DO - 10.1016/0014-2999(90)90469-M
M3 - Article
VL - 178
SP - 143
EP - 149
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -