Cerebrocrast

Kluša, Vija

doi:10.1358/dof.1995.020.02.284117

Cited by 225 publications

(96 citation statements)

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“…7) could be related to the neuroprotective action of low doses of cerebrocrast administered to rats and mice in vivo (0.005 -0.05 mg kg 21 i.p., i.v., and p.o.) (Klusa, 1995). Gammapyrone, glutapyrone, and diethone were without effect on Ca 2þ -induced PTP.…”

Section: Resultsmentioning

confidence: 91%

“…The different effects of cerebrocrast and diethone cannot be attributed to differences on their lipid solubility since they are both lipophilic compounds (Misãne et al, 1993;Klusa, 1995;Velena et al, 1997Velena et al, , 1999. The apparent partition coefficient of cerebrocrast, log P ¼ 4:96 (octanol/water) (Tirzite, personal communication) and that of diethone, log P .…”

Section: Discussionmentioning

confidence: 99%

“…Cerebrocrast [IOS-1.1212; 2-propoxyethyl ester of 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid] is a neuroprotector and cognition enhancer compound (Misãne et al, 1993;Klusa, 1995;Velena et al, 1997;Klegeris et al, 2002). Its molecule is characterized by increased lipophilicity due to both medium length 2-propoxy-ethyl side chains with oxa atoms in positions 3 and 5 of the DHP ring and the combination with the difluoromethoxygroup at position 2 of the phenyl ring which is joined to the DHP at position 4 (Misãne et al, 1993;Klusa, 1995;Velena et al, 1997;Klegeris et al, 2002). It is considered that this lipophilic molecule is capable of penetrating easily the blood -brain barrier, the plasma and organelles membranes, including those of mitochondria (Misãne et al, 1993;Klusa, 1995;Velena et al, 1997;Klegeris et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Its molecule is characterized by increased lipophilicity due to both medium length 2-propoxy-ethyl side chains with oxa atoms in positions 3 and 5 of the DHP ring and the combination with the difluoromethoxygroup at position 2 of the phenyl ring which is joined to the DHP at position 4 (Misãne et al, 1993;Klusa, 1995;Velena et al, 1997;Klegeris et al, 2002). It is considered that this lipophilic molecule is capable of penetrating easily the blood -brain barrier, the plasma and organelles membranes, including those of mitochondria (Misãne et al, 1993;Klusa, 1995;Velena et al, 1997;Klegeris et al, 2002). Gammapyrone [IOS-1.2134;4-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido) butyric acid] is a neuroprotector (Misãne et al, 1993), whereas glutapyrone [IOS-1.397; disodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido) glutarate] is an antiarrhythmic compound (Karpova et al, 1993;Klusa et al, 1996;Velena et al, 1997;Briede et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Effects of 1,4-dihydropyridine derivatives (cerebrocrast, gammapyrone, glutapyrone, and diethone) on mitochondrial bioenergetics and oxidative stress: a comparative study

Férnandes

2003

Mitochondrion

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The potential protective action of 1,4-dihydropyridine derivatives (cerebrocrast, gammapyrone, glutapyrone, and diethone) against oxidative stress was assessed on mitochondrial bioenergetics, inner membrane anion channel (IMAC), Ca 2þ -induced opening of the permeability transition pore (PTP), and oxidative damage induced by the oxidant pair adenosine diphosphate (ADP)/Fe 2þ (lipid peroxidation) of mitochondria isolated from rat liver. By using succinate as the respiratory substrate, respiratory control ratio (RCR), ADP to oxygen ratio (ADP/O), state 3, state 4, and uncoupled respiration rates were not significantly affected by gammapyrone, glutapyrone, and diethone concentrations up to 100 mM. Cerebrocrast at concentrations higher than 25 mM depressed RCR, ADP/O, state 3, and uncoupled respiration rates, but increased three times state 4 respiration rate. The transmembrane potential (DC) and the phosphate carrier rate were also decreased. At concentrations lower than 25 mM, cerebrocrast inhibited the mitochondrial IMAC and partially prevented Ca 2þ -induced opening of the mitochondrial PTP, whereas gammapyrone, glutapyrone, and diethone were without effect. Cerebrocrast, gammapyrone, and glutapyrone concentrations up to 100 mM did not affect ADP/Fe 2þ -induced lipid peroxidation of rat liver mitochondria, while very low diethone concentrations (up to 5 mM) inhibited it in a dose-dependent manner, as measured by oxygen consumption and thiobarbituric acid reactive substances formation. Diethone also prevented DC dissipation due to lipid peroxidation initiated by ADP/Fe 2þ . It can be concluded that: none of the compounds interfere with mitochondrial bioenergetics at concentrations lower than 25 mM; cerebrocrast was the only compound that affected mitochondrial bioenergetics, but only for concentrations higher than 25 mM; at concentrations that did not affect mitochondrial bioenergetics (#25 mM), only cerebrocrast inhibited the IMAC and partially prevented Ca 2þ -induced opening of the PTP; diethone was the only compound that expressed antioxidant activity at very low concentrations (#5 mM). Cerebrocrast acting as an inhibitor of the IMAC and diethone acting as an antioxidant could provide effective protective roles in preventing mitochondria from oxidative damage, favoring their therapeutic interest in the treatment of several pathological situations known to be associated with cellular oxidative stress.

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Section: Resultsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of 1,4-dihydropyridine derivatives (cerebrocrast, gammapyrone, glutapyrone, and diethone) on mitochondrial bioenergetics and oxidative stress: a comparative study

Férnandes

2003

Mitochondrion

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“…Благодаря наличию в структуре «крип-то» аминокислотных компонентов (β-аланина, NMDA), а также аналога дигидроникотинамида, формирующего дигидропиридиновый остов, это соединение рассматрива-ется как пептидомиметик. Цереброкраст не является ан-тагонистом кальция в нервной ткани (Kluša, 1995;Duburs et al, 2008), тем не менее, по данным Бриеде с соавтора-ми, при низкой концентрации (10 -6 М) он снижает вну-триклеточное содержание Ca 2+ в тромбоцитах на 9 %, а после их стимуляции тромбином -на 55 %; кроме того, он уменьшает гиперкальциемию на фоне диабета, вызван-ного стрептозотоцином у крыс (Briede et al, 2002;Briede et al, 2007). Оба соединения (цереброкраст и диэтон) по их сродству к рецепторам глюкокортикоидных гормонов отнесены к одной и той же группе производных 1,4-ДГП, проявляющих умеренный антагонизм по отношению к ионам кальция, при этом IC 50 составляет 40,7 ± 3,26 и 45,32 ± 2,27 мкМ соответственно, на порядок превы-шая этот показатель у типичных ингибиторов кальциевых каналов нифедипина и форидона (Vaitkuvienė et al, 2006).…”

Section: материалы и методыunclassified

Diludine and cerebrocrast as bioprotectors in the model test-systems in vivo

Savina

Nikitchenko

Dalivelya

et al. 2009

Ecological genetics

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An influence of two 1,4-dihydropyridine derivatives (diludine and cerebrocrast) on Drosophiladevelopment and germ cell mutability was studied. It was revealed the concentration range, within which the compounds manifest their bio-stimulating effects increasing individual survival by 50-80 % as well as the protective action against the alkylating agent ethyl methanesulfonate reducing the level of induced mutations by 30-50 %. The pattern and presumable mechanisms of the bioprotective action of these compounds are considered.

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Modification of swelling–contraction–aggregation processes in rat muscle mitochondria by the 1,4-dihydropyridines, cerebrocrast and glutapyrone, themselves and in the presence of azidothymidine

Velēna

Skujiņš

Svirskis

et al. 1997

Cell Biochem. Funct.

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The influence of the 1,4-dihydropyridines (DHPs), water-soluble glutapyrone available as sodium, potassium and ammonium salts of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-DHP-4-carboxamide)glutaric acid, from one side, and a lipophylic cerebrocrast, 2-propoxyethyl 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-DHP-3,5-dicarboxylate, from the other side, on partially damaged mitochondria of the Wistar rat hindlimb muscle was also studied. The following tests were made: (1) rates of endogenous respiration and substrate (succinate) oxidation and oxidative phosphorylation; (2) rates and amplitudes of high-amplitude swelling and contraction after the addition of ATP, ADP and succinate to the previously swollen mitochondria and (3) rate of reversible self-aggregation of mitochondria isolated in salt media after ATP-induced contraction without and in the presence of azidothymidine (AZT). Cerebrocrast (10-100 microM) partially normalized the endogenous respiration rate and slightly augmented the respiration rate after the addition of succinate and to lesser extent ADP. Cerebrocrast in a concentration-dependent manner (2.5-50 microM) increased (two-fold at 20-50 microM) the active contraction amplitude of swollen mitochondria, induced by single or repeated additions of ATP. The influence of cerebrocrast on the ADP- and succinate-induced contractions was less obvious. Unlike cerebrocrast glutapyrone caused a reduction of the ATP-induced contraction amplitude (two-fold at 0.5-5.0 mM), not impairing the mitochondrial contraction ability in response to ATP or succinate. Pre-exposure to 2.5 mM glutapyrone resulted in at least a 10-fold inhibition of the reversible aggregation rate in the presence of 99 and 198 microM AZT. The results suggest the usefulness of further study of cerebrocrast and glutapyrone in preventing AZT-induced and some other mitochondrial myopathies.

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Cerebrocrast

Cited by 225 publications

References 0 publications

Effects of 1,4-dihydropyridine derivatives (cerebrocrast, gammapyrone, glutapyrone, and diethone) on mitochondrial bioenergetics and oxidative stress: a comparative study

Effects of 1,4-dihydropyridine derivatives (cerebrocrast, gammapyrone, glutapyrone, and diethone) on mitochondrial bioenergetics and oxidative stress: a comparative study

Diludine and cerebrocrast as bioprotectors in the model test-systems in vivo

Modification of swelling–contraction–aggregation processes in rat muscle mitochondria by the 1,4-dihydropyridines, cerebrocrast and glutapyrone, themselves and in the presence of azidothymidine

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