Effect of propentofylline on the GABA system of a rat brain

Vukadinovića, Vidoje; Stefanovich, V.; Rakića, Ljubiša

doi:10.1002/ddr.430070108

Cited by 14 publications

(3 citation statements)

References 29 publications

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“…On the other hand, inhibition of adenosine uptake and metabolism [11] by dipyridamole alone could produce also protection of the rat brain against the ischemic insult combined with an increased GABA level. Similar results have been reported where propentofylline, an inhibitor of adenosine uptake, was found to increase GABA level in the brain [19] and to reduce glutamate release during and after ischemia [20]. In addition, adenosine agonists were found to reduce hypoxic neuronal injury both in vivo [21] and in vitro [22].…”

Section: Discussionsupporting

confidence: 86%

Influence of Inhibition of Adenosine Uptake on the γ-Aminobutyric Acid Level of the Ischemic Rat Brain

Seif-El-Nasr

Khattab²

2011

Arzneimittelforschung

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Loss of inhibitory GABAergic modulation may induce hyperexcitability of neuronal elements and potentiate their vulnerability to excitotoxic injury. It has been also found that the adenosine system interacts with the GABAergic system during ischemia and anoxia where the adenosine receptors as well as the GABAergic receptors may conscript the same intracellular pathway to increase tolerance to ischemia. Therefore, it was aimed to study whether dipyridamole (CAS 58-32-2), an adenosine uptake inhibitor, or adenosine (CAS 58-61-7) could affect the rat brain gamma-aminobutyric acid (GABA, CAS 56-12-2) level after induction of cerebral ischemia, and to test their effect on the lactate dehydrogenase (LDH) activity of the ischemic rat brain. Ischemia was induced by bilateral clamping of the common carotid arteries for 60 min followed by reperfusion for other 60 min. Dipyridamole was administered alone and in combination with adenosine and the effect of the drugs on the brain GABA level as well as on LDH activity was determined. The results show that dipyridamole could protect the brain of rats against the ischemic insult, while adenosine when administered separately failed to influence the selected parameters. Protection of the rat brain by dipyridamole might be related to the elevated level of GABA.

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Section: Discussionsupporting

confidence: 86%

Influence of Inhibition of Adenosine Uptake on the γ-Aminobutyric Acid Level of the Ischemic Rat Brain

Seif-El-Nasr

Khattab²

2011

Arzneimittelforschung

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“…It acts as combined inhibitor of both adenosine transporter and phosphodiesterases. Propentofylline plays significant role in increasing the cerebral concentration of γ-aminobutyric acid (GABA) and adenosine while treating ischemia [ 98 , 99 ]. It acts as neuroprotective glial cell modulator which suppresses the neurotoxic effects of microglial cells and thus restores the functions of astrocytes [ 100 , 101 ].…”

Section: Main Textmentioning

confidence: 99%

Xanthine scaffold: scope and potential in drug development

Singh

Shreshtha

Thakur

et al. 2018

Heliyon

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Medicinal plants have been the basis for discovery of various important marketed drugs. Xanthine is one such lead molecule. Xanthines in various forms (caffeine, theophylline, theobromine, etc) are abode in tea, coffee, cocoa, chocolate etc. giving them popular recognition. These compounds are best known for their diverse pharmaceutical applications as cyclic nucleotide phosphodiesterase inhibition, antagonization of adenosine receptor, anti-inflammatory, anti-microbial, anti-oxidant and anti-tumor activities. These properties incentivize to use xanthine as scaffold to develop new derivatives. Chemical synthesis contributes greater diversity in xanthine based derivatisation. With highlighting the existing challenges in chemical synthesis, the present review focuses the probable solution to fill existing lacuna. The review summarizes the available knowledge of xanthine based drugs development along with exploring new xanthine led chemical synthesis path for bringing diversification in xanthine based research. The main objective of this review is to explore the immense potential of xanthine as scaffold in drug development.

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“…Long-term potentiation of hippocampal slices is enhanced by propentofylline in guinea pigs (Tanaka et al, 1990). After administration ofpropentofylline the concentration of y-aminobutyric acid (GABA) incrases in cortex, N. caudatus and thalamus in a rat model (Vukadinovic et al, 1986). Derivatives of GABA are, however, widely used as nootropic agents and have been reported to improve cognition in different forms of dementia, including dementia of the Alzheimer type (Maina et al, 1989 andBaumel et al, 1989).…”

Section: Wirksamkeit Des Xanthin-derivates Propentofyliin Bei Dementimentioning

confidence: 99%

Placebo-Controlled Trial of the Xanthine Derivative Propentofylline in Dementia

Möller

Maurer

Saletu³

1994

Pharmacopsychiatry

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Treatment of dementing illnesses is still unsatisfactory and agents that might have potential for improving cognitive functions are therefore under extensive investigation. Over a 3-month period a multicenter, double-blind, placebo-controlled, parallel-group study was conducted in 190 patients with dementia to examine whether administration of the xanthine derivative propentofylline at 0.9 g/d might either improve cognition or slow the progression of the disease. Improvement in performance on the Gottfries-Brane-Steen scale (GBS) and in at least two of eight psychometric assessments were defined a priori as the primary efficacy measures. The total scores on the GBS decreased in both the propentofylline and the placebo groups, with improvement however being significantly (p < 0.0001) higher in the propentofylline group. The mean scores in the Mini-Mental State Examination increased significantly (p < 0.05) in both groups, but the increase was significantly (p < 0.02) higher in the propentofylline-treated group. In contrast, psychometric assessments and the cognitive difficulties scale failed to demonstrate a therapeutic benefit of propentofylline after three months. Performance in these categories showed a significant (p < 0.05) improvement for the propentofylline-treated patients and for the placebo-treated patients, but was comparable for both groups. Thus, in spite of the positive results in GBS, the efficacy of propentofylline could not be established according to the definition of the primary efficacy measures. The clinical parameters, however, can be positively influenced by propentofylline. In addition, the results indicate that patient performance can already be enhanced if subjects are required to engage in cognitive tasks.

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Effect of propentofylline on the GABA system of a rat brain

Cited by 14 publications

References 29 publications

Influence of Inhibition of Adenosine Uptake on the γ-Aminobutyric Acid Level of the Ischemic Rat Brain

Influence of Inhibition of Adenosine Uptake on the γ-Aminobutyric Acid Level of the Ischemic Rat Brain

Xanthine scaffold: scope and potential in drug development

Placebo-Controlled Trial of the Xanthine Derivative Propentofylline in Dementia

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