Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia

Mitochondrial disturbances, excitotoxicity, neuroinflammation and kynurenines: Novel therapeutic strategies for neurodegenerative disorders

“…Besides halogenation, a further possibility for the pharmaceutical modification of KYNA is amidation at the carboxyl moiety. One of our KYNA amides, N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride, exerted protective effects both in the four-vessel occlusion model of cerebral ischemia (rats; [71]) and in the N171-82Q transgenic mouse model of HD [72].…”

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

“…Accordingly, one of the KYNA amide compounds synthesized by our group, N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride exerted protective effects both in the N171-82Q transgenic mouse model of Huntington's disease and the four-vessel occlusion model of cerebral ischemia in rats [310,311]. At the dose capable of exerting these neuroprotective effects, the KYNA analog did not demonstrate any significant systemic side effects, i.e., it did not alter locomotor activity, working memory performance, and long-lasting, consolidated reference memory in contrast to the observed indirect side-effects following KYN administration [312][313][314].…”

Excitotoxic Mechanisms in Non-Motor Dysfunctions and Levodopa- Induced Dyskinesia in Parkinson's Disease: The Role of the Interaction Between the Dopaminergic and the Kynurenine System

“…In an animal model of transient global forebrain ischaemia, KYNA exerted a neuroprotective effect by reducing the hippocampal CA1 pyramidal cell loss. The analogue was effective both as a pretreatment and as post-treatment 96 . In a transgenic mice model of Huntington's disease, the same analogue proved not only to ameliorate the motor symptoms but it also significantly, by more than 30%, prolonged the survival of the animals.…”

“…The synthethic KYNA analogues have already been tested in several animal models of neurological diseases with promising results 95,96 . In an animal model of transient global forebrain ischaemia, KYNA exerted a neuroprotective effect by reducing the hippocampal CA1 pyramidal cell loss.…”