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Dihydroergotamine Increases Histamine Brain Levels and Improves Memory in a Scopolamine-Induced Amnesia Model.
Hernández-Rodríguez, Maricarmen; Mera Jiménez, Elvia; Nicolás-Vázquez, María Inés; Miranda-Ruvalcaba, Rene.
Affiliation
  • Hernández-Rodríguez M; Laboratorio de Cultivo Celular, Neurofarmacología y Conducta, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Ciudad de México 11340, Mexico.
  • Mera Jiménez E; Laboratorio de Cultivo Celular, Neurofarmacología y Conducta, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Ciudad de México 11340, Mexico.
  • Nicolás-Vázquez MI; Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo s/n, Colonia Santa María las Torres, Cuautitlán Izcalli 54740, Mexico.
  • Miranda-Ruvalcaba R; Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo s/n, Colonia Santa María las Torres, Cuautitlán Izcalli 54740, Mexico.
Int J Mol Sci ; 25(7)2024 Mar 26.
Article in En | MEDLINE | ID: mdl-38612521
ABSTRACT
The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Scopolamine / Dihydroergotamine Limits: Animals Language: En Journal: Int J Mol Sci Year: 2024 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Scopolamine / Dihydroergotamine Limits: Animals Language: En Journal: Int J Mol Sci Year: 2024 Document type: Article Affiliation country:
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