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Paradoxical disinhibition is a paradoxical reaction, an uncommon but recognized phenomenon, characterized by acute excitement and an altered mental state, caused by benzodiazepines. The mechanism is poorly known, but the most accepted theory is that it occurs secondary to inhibition of the restraining influences of the cortex and frontal lobe due to the GABA-mimetic action of benzodiazepines. Reversal of this action could be attained by an NMDA-receptor antagonist, ketamine.
Mechanism
It is thought that blockage of presynasptic GABA receptors of GABAergic neurons induce stimulation as a net effect, because the action of the most powerful inhibitory neurotransmitter, GABA, is blocked.
References
- Neale, G; Smith, A J (May 2007). "Self-harm and suicide associated with benzodiazepine usage". British Journal of General Practice. 57 (538): 407–8. PMC 2047018. PMID 17504594.
- Mohammad Golparvar; Mahmood Saghaei; Parvin Sajedi; Seid Sajad Razavi (13 October 2004). "Paradoxical reaction following intravenous midazolam premedication in pediatric patients – a randomized placebo controlled trial of ketamine for rapid tranquilization" (PDF). Pediatric Anesthesia. 14 (11): 924–930. doi:10.1111/j.1460-9592.2004.01349.x. PMID 15500492. S2CID 21243795. Archived from the original (PDF) on 25 April 2012.
- Kaplan Step 1 2010 Video, Pharmacology, Sec04. Ch01A, "Sedative, Hypnotic, Anxiolytic Drugs"