Targeting the Mitochondria by Novel Adamantane-Containing 1,4-Dihydropyridine Compounds

Linda Klimaviciusa1, Maria A. S. Fernandes2, Nelda Lencberga1, Marta Pavasare1, Joaquim A. F. Vicente2, Antonio J. M. Moreno2, Maria S. Santos3, Catarina R. Oliveira4, Imanta Bruvere5, Egils Bisenieks5, Brigita Vigante5 and Vija Klusa1 1Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga 2IMAR-CMA, Department of Life Sciences, University of Coimbra, Coimbra 3CNC, Department of Life Sciences, University of Coimbra, Coimbra 4CNC, Faculty of Medicine, University of Coimbra, Coimbra 5Laboratory of Membrane Active and beta-Diketone Compounds, Latvian Institute of Organic Synthesis, Riga 2,3,4Portugal 1,5Latvia

Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives

The novel 1,4-dihydropyridine derivatives containing the cationic pyridine moiety at the position 4, and the N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle were designed, synthesised, and assessed in biological tests. Among all the novel compounds, the 4-(N-dodecyl) pyridinium group-containing compounds 11 (without the N-propargyl group) and 12 (with the N-propargyl group) demonstrated the highest calcium antagonistic properties against neuroblastoma SH-SY5Y (IC50 about 5–14 mM) and the vascular smooth muscle A7r5 cell (IC50 – 0.6–0.7 mM) lines, indicating that they predominantly target the L-type calcium channels. These compounds showed a slight total antioxidant act…

Anti-Neurotoxic Effects of Tauropyrone, a Taurine Analogue

Evaluation of “Stress Relief” Dietary Supplement on Animal Stress Level and Locomotion

Abstract Search of new approaches for harmless, non-medication treatment of body dysfunctions is still on the agenda of vet and human practitioners and researchers as well. This study presents evaluation of the effect of “Stress Relief” dietary supplement (SR) on mice behaviour under different acute short-term stress conditions and treatment duration. Five experiments were performed and in each 40 animals were randomly split into four (I–IV) groups, where I and II — non-stressed mice, III and IV — stressed animals, I and III received water with trace mineral solution (TMS), II and IV received water with SR. As stress factors, forced swimming, rodent predator odour or both together were appl…

The effects of glutamate receptor antagonists on cerebellar granule cell survival and development.

N-Methyl-d-aspartate (NMDA) receptor stimulation promotes neuronal survival and differentiation under both in vitro and in vivo conditions. We studied the effects of various NMDA receptor antagonists acting at different NMDA receptor binding sites and non-NMDA receptor antagonists on the development and survival of cerebellar granule cell (CGC) culture. Only three of the drugs tested induced neurotoxicity-MK-801 (non-competitive NMDA channel blocking antagonist), ifenprodil (an antagonist of the NR2B site and polyamine site of the NMDA receptor) and L-701.324 (full antagonist at glycine site), while CGP-37849 (a competitive NMDA antagonist), (+)-HA-966 (a partial agonist of the glycine site…

Distinct effects of atypical 1,4-dihydropyridines on 1-methyl-4-phenylpyridinium-induced toxicity.

Our previous data obtained from in vivo experiments demonstrated high neuroprotective effects of three novel atypical neuronal non-calcium antagonistic 1,4-dihydropyridine (DHP) derivatives cerebrocrast, glutapyrone and tauropyrone. The present studies were carried out in vitro to clarify, at least in part, their mechanism of action in primary culture of cerebellar granule cells by use of 1-methyl-4-phenylpyridinium (MPP+) as a neurotoxic agent which causes dramatic oxidative stress. Cerebrocrast (highly lipophilic, with a classical two-ring structure) dose-dependently (0.01-10.0 microM, EC50 = 13 nM) reduced MPP+-induced cell death. At the same time, the calcium antagonist nimodipine (refe…