脳のシステム工学・制御理論的観点から考察する精神病のメカニズム 第11報 睡眠薬・抗不安薬の機序と問題点の考察/An Examination of the Mechanisms of Psychosis from the Perspective of Systems Engineering and Control Theory of the Brain Report No. 11: An Examination of the Mechanisms and Issues Surrounding Hypnotics and Anxiolytics

【Abstract (English)】Although sleeping pills and anti-anxiety drugs differ in their intended purposes and the conditions for which they are indicated, they are essentially a class of related drugs that share the common mechanism of action: direct and allosteric effects on GABA (γ-aminobutyric acid) receptor complexes (particularly GABA-A and GABA-B receptors). Just as alcohol (ethanol) stimulates multiple systems of GABA receptors in the brain to produce anxiolytic and central depressant effects, these drugs directly induce the influx of Cl⁻ (chloride ions) without the mediation of alcohol, thereby forcing the nervous system into a state of sedation. Based on this theory (the model in which GABA action promotes synaptic pruning via an anxiolytic response), these drugs act as physical factors that drive excessive synaptic pruning in the prefrontal cortex with 100 per cent certainty. When administered to minors or patients with ‘genetic predisposition to stress (vulnerability to developmental disorders)’, they rapidly exacerbate schizophrenia-like pathology and inevitably induce dissociative episodes associated with disinhibition, somnambulistic abnormal behaviour, impulsive suicide, and even criminal behaviour. 【概要(日本語)】睡眠薬および抗不安薬は、目的や適応病名が異なるものの、本質的にはGABA(γ-アミノ酪酸)受容体複合体(特にGABA-A受容体およびGABA-B受容体)への直接的・アロステリックな作用を共通の目的とする同系薬剤である。 アルコール(エタノール)が脳内で多系統のGABA受容体を刺激して抗不安・中枢抑制をもたらすのと同様に、これらの薬剤はアルコールを仲介することなく直接的にCl⁻(塩化物イオン)の流入を誘導し、神経系を強制的な鎮静状態へと移行させる。本理論(GABA作用が抗不安応答を介してシナプス刈り込みを促進するモデル)に基づけば、これらの薬剤は前頭葉シナプスの過剰刈り込みを100%確実に推し進める物理的因子となる。未成年者や「ストレスに弱い遺伝特性(発達障害的脆弱性)」を有する患者に投与した場合、統合失調症的病理を急速に悪化させ、脱抑制に伴う解離性発作、夢遊病状異常行動、衝動的自殺、さらには犯罪行動を不可避的に誘発する。