Screening of novel pentacyclo-undecylamines for neuroprotective activity.
A novel series of pentacyclo-undecylamines with 8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane (NGP1-01) as the lead compound was synthesised and screened for neuroprotective activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian mouse model. We hypothesise that these compounds may attenuate excitotoxic neuronal cell death mediated through the NMDA receptor (similar to memantine), and through calcium channel block. The pentacyclo-undecylamines (300 mg/kg) were administered to C57BL/6 mice 30 min before intraperitoneal (i.p.) MPTP administration (35 mg/kg). Striatal dopamine, 3,4-hydroxyphenylacetic acid (DOPAC), and homovanillic acid levels were analysed 10 days later by means of HPLC with electrochemical detection. Increased levels of DOPAC and homovanillic acid were observed when some of the test compounds were administered together with MPTP (compared to animals receiving only MPTP). One compound in the series, 8-phenylethylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane, attenuated MPTP-induced striatal dopamine depletion when compared to animals treated with MPTP only (p<0.05).
Geldenhuys
Werner J
WJ
Department of Pharmaceutical Chemistry, Potchefstroom University for Christian Higher Education, Private Bag X6001, 2531, Potchefstroom, South Africa.
Terre'Blanche
Gisella
G
Van der Schyf
Cornelis J
CJ
Malan
Sarel F
SF
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*
D000588:Amines; D015259:Dopamine Agents; D018696:Neuroprotective Agents; D011083:Polycyclic Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D016291:Dizocilpine Maleate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid