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La conjugaison à l'acide ascorbique augmente la disponibilité cérébrale de l'acide carboxylique de losartan et protège contre le parkinsonisme chez le rat.

L’identification du système rénine-angiotensine dans l’interaction de l’hypertension et de la neurodégénérescence a ouvert la voie à la réutilisation des médicaments antihypertenseurs contre le parkinsonisme. L'acide carboxylique de losartan (LCA), le métabolite puissant du bloqueur AT1 en tant que bloqueur de l'AT1, souffre d'une faible biodisponibilité et d'un faible accès au cerveau. Comme les transporteurs d'ascorbate ont déjà montré suffisamment de souplesse en tant que transporteurs, nous avons conjugué l'acide losartan carboxylique à l'acide ascorbique dans le but d'obtenir une plus grande disponibilité orale / cérébrale. L'ester de LCA et d'acide ascorbique (FED) a été développé en tenant compte de la spécificité du substrat des transporteurs d'ascorbate. La biodisponibilité orale / cérébrale a été évaluée à l'aide d'un modèle pharmacocinétique in vivo. L'effet sur le système nerveux central (SNC) et la protection contre le parkinsonisme ont été évalués à l'aide de modèles in vivo. Biodisponibilité améliorée de la LCA par la FED. La plus grande disponibilité cérébrale de l'ACL a permis la protection du SNC, comme en témoigne l'augmentation de l'activité locomotrice, l'amélioration de la coordination motrice et la protection contre la catatonie induite par les médicaments. En conclusion, FED propose une approche pour réutiliser l'ACV contre le parkinsonisme. Cela peut encourager des investigations supplémentaires pour traiter simultanément l'hypertension et la neurodégénérescence.


Source: https://www.ncbi.nlm.nih.gov/pubmed/30350232


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