A dihydropyridine conjugate which generates high and sustained levels of the corresponding pyridinium salt in the brain does not exhibit neurotoxicity in cynomolgus monkeys
| Autor: | Robert J. Perchalski, Nicholas Bodor, Marcus E. Brewster, Kerry S. Estes |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
Dihydropyridines
medicine.medical_specialty medicine.drug_class Dopamine Neurotoxins Pyridinium Compounds chemistry.chemical_compound Internal medicine medicine Animals Monoamine Oxidase Dose-Response Relationship Drug Estradiol Chemistry General Neuroscience Dopaminergic Dihydropyridine Neurotoxicity Brain Rats Inbred Strains Luteinizing Hormone Pargyline medicine.disease Rats Macaca fascicularis Endocrinology Monoamine neurotransmitter Estrogen 3 4-Dihydroxyphenylacetic Acid Macaca Female Pyridinium Luteinizing hormone medicine.drug |
| Zdroj: | Neuroscience Letters. 87:277-282 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/0304-3940(88)90461-2 |
| Popis: | Many drugs can be selectively delivered to the brain by using a dihydropyridine in equilibrium pyridinium salt chemical delivery system (CDS). The interaction of these systems with central dopaminergic function was examined in this communication. Castrate female Sprague-Dawley rats when treated with a CDS for estradiol (i.e. 3-hydroxy-17 beta-[( (1-methyl-1,4-dihydropyridin-3-yl)carbonyl]oxy) estra-1,3,5(10)-triene or E2CDS) exhibit sustained and profound suppression of serum levels of leuteinizing hormone (LH). Treatment of rats with pargyline (80 mg/kg) prior to E2CDS (2 mg/kg) did not mitigate the biological effectiveness of this estrogen indicating at least indirectly that monoamine oxidate (MAO) was not involved in the CDS activation. In a more direct examination, cynomolgus monkeys treated with various repeated doses of E2CDS (cumulative doses of 0.2-40.0 mg/kg) demonstrated neither impaired motor function nor depleted striatal dopamine concentrations. The latter parameter was measured using liquid chromatographic-electrochemical analysis. These experiments support the contention that the CDS is not neurotoxic and further strengthens the strict structure-activity requirements for MPTP-induced neurotoxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|