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(g/kg) (g/kg) 16 12 6 5 4 3 2 1 8 4 A/A A/G+G/G OPRM1 Fukuda et al., Pain, 21 C/C C/T T/T ADRB2 () Fentanyl requirement (μg/kg; ln-transformed) (g/kg) 1.4 1.2 1.1.8.6.4.2 Nishizawa et al., PLoS ONE, 21 12 1 8 6 4 2 C/C C/T T/T C/C C/T T/T (n = 2) (n = 36) (n = 29) GIRK2 rs2835859 Genotype A/A A/G+G/G SSRO355 PCAPatient-controlled analgesia 124 Infinium assay IIiScan system Human1M-Duo (GWAS3) 3 Additive/Dominant/Recessive models [ FDR False Discovery RateQ] <.5
Chromosome 1 2 3 4 5 6 7 8 9 1 11 12 13 14 15 16 17181922122 X CC/C, C/T +C/C genotype n = 194 P <.5 n = 436 P <.5 Postoperative analgesic use (μg/kg; log-transformed) 2 1.8 1.6 1.4 1.2 1.8.6.4.2 * T/T T/C C/C rs2952768 genotype *: corrected P <.5. Postoperative analgesic use (μg/kg; log-transformed) 1.9.8.7.6.5.4.3.2.1 T/T T/C C/C rs2952768 genotype : P <.5. n = 221 n = 221.5 < P <.1 C n = 5 Temperament and Character Inventory: TCI Reward Dependence: RD P <.5 P <.5
anterior cingulate cortex RNA DNA1 Relative mrna expression.4.3.3.2.2.1.1. * (P =.1197) T/T T/C C/C rs2952768 genotype (Nishizawa et al., Mol Psychiatry, 214) 24 y (μg/kg) y = -.667 + (-.6) [(year)] +.194 [] +.12 [(cm)] + (-.7) [(kg)] + (-.88) [ ()] +.213 [1] +.241 [2] +.183 [3] +.247 [4] +.542 [5] 21112
195 Chlorpromazine Marketed in France (1952) USA (1954) Henri Laborit (1914-1995) French Neurosurgeon Jean Delay (197 1987) Pierre Deniker (1917-1998) Sainte-Anne mental hospital in Paris ECT Insulin Shock Evolution of Psychotropic Drugs Chlorpromazine 1st-generation antipsychotics Haloperidol Fluphenazine Thioridazine Loxapine Perphenazine 2nd-generation antipsychotics Clozapine Risperidone Olanzapine Quetiapine Ziprasidone Aripiprazole Next-generation Bifeprunox Asenapine Iloperidone Lurasidone LY21423 3s 4s 5s 6s 7s 8s 9s 2 1 Imipramine Clomipramine Nortriptyline Amitriptyline Desipramine Phenelzine Isocarboxazid Trancylcypromine (TCAs) 1st-generation Antidepressants Maprotiline Amoxapine Trazodone 2nd-generation Antidepressants Fluoxetine Sertraline Paroxetine Fluvoxamine Citalopram (SSRI) Bupropion 3rd-generation Antidepressants Nefazodone Mirtazapine (NaSSA) Venlafaxine Milnacipran (SNRI) Duloxetine Escitalopram Agomelatine 4th-generation Antidepressants Vortioxetine Vilazodone Levomilnacipran Next-generation
NMDA Yamakura et al. Neuroreport 1993 Yamamoto et al. Curr Mol Med 215 GluN 2A 2B 2C Watanabe et al. Neuroreport 1992 2D 1 Ikeda et al, FEBS Lett 1992 Ikeda et al. Mol Brain Res 1995 GluN2D GluN2D PCP DA (AUC) 8 6 4 2 Wild 2A -/- 2D -/- Saline Wild 2A -/- 2D -/- PCP Hagino et al. PLoS ONE 21 PCP-KO (46) 1 PCP-W (193) Compared to saline control 15 9 26 PCP-KO (81) KO/W (247) 21 3 Ratio Gene expressions (% of saline control) PCP-W, PCP-injected wild-type mice compared to saline-injected wild-type mice. PCP-KO, PCP-injected GluN2D KO mice compared to saline-injected wild-type mice. KO/W, saline-injected GluN2D KO mice compared to saline-injected wild-type mice. Effect of PCP in KO mice 2 15 1 5 = -.564 Weak inverse relationship 5 1 15 2 25 Gene expressions Effect of PCP in Wild mice <.7-fold Yamamoto et al. > 1.3-fold Mol Brain 213
GluN2D GluN2D PCP Yamamoto et al. Neuropharmacology 216 Yamamoto et al. Neurosci Lett 215
Chair Kazutaka Ikeda Vice Chair Kazutaka Shimoda Vice Chair Toshiyuki Someya JSCNP Meeting Chair Reiji Yoshimura JSNP Meeting Chair Hisatsugu Miyata