{"doi":"10.3389/fphar.2021.668285","title":"D-Amphetamine Rapidly Reverses Dexmedetomidine-Induced Unconsciousness in Rats","abstract":"D-amphetamine induces emergence from sevoflurane and propofol anesthesia in rats. Dexmedetomidine is an α 2 -adrenoreceptor agonist that is commonly used for procedural sedation, whereas ketamine is an anesthetic that acts primarily by inhibiting NMDA-type glutamate receptors. These drugs have different molecular mechanisms of action from propofol and volatile anesthetics that enhance inhibitory neurotransmission mediated by GABA A receptors. In this study, we tested the hypothesis that d-amphetamine accelerates recovery of consciousness after dexmedetomidine and ketamine. Sixteen rats (Eight males, eight females) were used in a randomized, blinded, crossover experimental design and all drugs were administered intravenously. Six additional rats with pre-implanted electrodes in the prefrontal cortex (PFC) were used to analyze changes in neurophysiology. After dexmedetomidine, d-amphetamine dramatically decreased mean time to emergence compared to saline (saline:112.8 ± 37.2 min; d-amphetamine:1.8 ± 0.6 min, p < 0.0001). This arousal effect was abolished by pre-administration of the D 1 /D 5 dopamine receptor antagonist, SCH-23390. After ketamine, d-amphetamine did not significantly accelerate time to emergence compared to saline (saline:19.7 ± 18.0 min; d-amphetamine:20.3 ± 16.5 min, p = 1.00). Prefrontal cortex local field potential recordings revealed that d-amphetamine broadly decreased spectral power at frequencies <25 Hz and restored an awake-like pattern after dexmedetomidine. However, d-amphetamine did not produce significant spectral changes after ketamine. The duration of unconsciousness was significantly longer in females for both dexmedetomidine and ketamine. In conclusion, d-amphetamine rapidly restores consciousness following dexmedetomidine, but not ketamine. Dexmedetomidine reversal by d-amphetamine is inhibited by SCH-23390, suggesting that the arousal effect is mediated by D 1 and/or D 5 receptors. These findings suggest that d-amphetamine may be clinically useful as a reversal agent for dexmedetomidine.","journal":"Frontiers in Pharmacology","year":2021,"id":171646,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":360644,"name":"Edlyn R. Zhang","orcid":"0000-0001-9517-7113","position":1,"is_corresponding":false},{"id":706460,"name":"Olivia G. Mallari","orcid":"0009-0004-4434-4654","position":2,"is_corresponding":false},{"id":360643,"name":"Olivia A. Moody","orcid":"0000-0002-9589-235X","position":3,"is_corresponding":false},{"id":522197,"name":"Kathleen F. Vincent","orcid":"0000-0001-6098-9998","position":4,"is_corresponding":false},{"id":706461,"name":"Eric D. Melonakos","orcid":"0000-0002-3643-9838","position":5,"is_corresponding":false},{"id":707079,"name":"Morgan J. Siegmann","orcid":null,"position":6,"is_corresponding":false},{"id":706462,"name":"Christa J. Nehs","orcid":"0000-0002-6708-1656","position":7,"is_corresponding":false},{"id":280811,"name":"Timothy T. Houle","orcid":"0000-0001-9584-5580","position":8,"is_corresponding":false},{"id":270289,"name":"Oluwaseun Akeju","orcid":"0000-0002-6740-1250","position":9,"is_corresponding":false},{"id":343787,"name":"Ken Solt","orcid":"0000-0001-5328-2062","position":10,"is_corresponding":false},{"id":362531,"name":"Risako Kato","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:46:33.067299Z","pmid":"34084141","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}