The effects of memantine on recovery, cognitive functions, and pain after propofol anesthesia / Efeitos da memantina sobre a recuperação, funções cognitivas e dor após a anestesia com propofol

Abstract Objectives: Postoperative cognitive dysfunction refers to the problems associated with thought and memory that are often experienced after major surgery. The aim of this study is to evaluate the effects of intraperitoneally administered memantine on recovery, cognitive functions, and pain after propofol anesthesia. Methods: The study was conducted in Gazi University Animal Research Laboratory, Ankara, Turkey in January 2012. Twenty-four adult female Wistar Albino rats weighing 170-270 g were educated for 300 s in the radial arm maze (RAM) over three days. Group P was administered 150 mg kg−1 of intraperitoneal (IP) propofol; Group M was given 1 mg kg−1 of IP memantine; and Group MP was given 1 mg kg−1 of IP memantine before being administered 150 mg kg−1 of IP propofol. The control group received only IP saline. RAM and hot plate values were obtained after recovery from the groups that received propofol anesthesia and 30 min after the administration of drugs in other two groups. Results: The duration of recovery for Group MP was significantly shorter than Group P (p < 0.001), and the number of entries and exits in the RAM by Group MP was significantly higher during the first hour when compared to Group P (p < 0.0001). Hot plate values, on the other hand, were found to be significantly increased in all groups when compared to the control values, aside from Group C (p < 0.0001). Conclusion: In this study, memantine provided shorter recovery times, better cognitive functions, and reduced postoperative pain. From this study, we find that memantine has beneficial effects on recovery, cognitive functions, and pain after propofol anesthesia.

Resumo Objetivos: A disfunção cognitiva no pós-operatório refere-se a problemas associados ao pensamento e à memória que são frequentemente manifestados após uma cirurgia de grande porte. O objetivo deste estudo foi avaliar os efeitos da memantina administrada por via intraperitoneal sobre a recuperação, as funções cognitivas e a dor após a anestesia com propofol. Métodos: O estudo foi feito no Laboratório de Pesquisa com Animais da Universidade de Gazi, Ankara, Turquia, em janeiro de 2012. Vinte e quatro ratos albinos do sexo feminino, adultos, da linhagem Wistar, com 170-270 g, foram treinados durante 300 segundos no labirinto radial de oito braços (LRB) durante três dias. O Grupo P recebeu 150 mg/kg−1 de propofol por via intraperitoneal (IP), o Grupo H recebeu 1 mg/kg−1 de memantina IP e o Grupo MP recebeu 1 mg/kg−1 de memantina IP antes da administração de 150 mg/kg−1 de propofol (IP). O grupo controle recebeu apenas solução salina IP. Os valores do LRB e da placa quente foram obtidos após a recuperação dos grupos que receberam propofol e 30 minutos após a administração dos fármacos nos outros dois grupos. Resultados: O tempo de recuperação do Grupo MP foi significativamente menor do que o do Grupo P (p < 0,001) e o número de entradas e saídas do LRB do Grupo MP foi significativamente maior durante a primeira hora, em comparação com o Grupo P (p < 0,0001). Os valores da placa quente, por outro lado, foram significativamente maiores em todos os grupos, em comparação com os valores do grupo controle, exceto pelo Grupo C (p < 0,0001). Conclusão: No presente estudo, memantina proporcionou tempos mais curtos de recuperação, funções cognitivas melhores e reduziu a dor no pós-operatório. A partir deste estudo, descobrimos que a memantina tem efeitos benéficos sobre a recuperação, as funções cognitivas e a dor após anestesia com propofol.

Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of rats exposed to cold stress

OBJECTIVES: Memantine is an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist used to treat Alzheimer's disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress. METHOD: We used male EPM-Wistar rats (n=40) divided into 4 groups: 1) Matched control (CON); 2) Memantine-treated rats (MEM); 3) Rats undergoing induced hypothermia (IH) and 4) Rats undergoing induced hypothermia that were also treated with memantine (IHM). Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of - 8ºC on the last day of the study. RESULTS: The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 μm³ vs. CON: 142 ± 2.3 μm³; p<0.05), while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 μm³) compared to the IH group (108 ± 1.7 μm³; p<0.05). CONCLUSION: Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress.

Evaluation of effects of memantine on cerebral ischemia in rats

To evaluate the effects of memantine on infarct size in cerebral ischemia and on neurological outcome after temporary middle cerebral artery occlusion [MCAO] and reperfusion in rats. In this study, performed between 2002-2004 in Dicle University School of Medicine, Diyarbakir, Turkey, 30 adult Sprague-Dawley rats were used. Cerebral ischemia was constituted by the intraluminal filament method with a 4-0 nylon suture. Reperfusion was started after 2 hours of MCAO. The rats were randomly divided into 2 groups as control and memantine. Saline 0.9% [0.5 ml/kg] and memantine [30 mg/kg] were administered via nasogastric intubations. Three coronal slices of 2 mm thickness were obtained from cerebrum, cerebellum, and brain stem, and were stained with a 2% solution of triphenyltetrazolium chloride. Transparent sheets were placed over each section and the areas of the brain and infarct were measured. Forty-five slices from each group [total 90] were obtained. Percent of ischemic area [%] in cerebrum, cerebellum, and brain stem level in memantine was lower than those of the control group [p=0.0001]. In addition, we determined an improvement in neurological score at 24th and 72nd hours in the rats that have been given memantine. The memantine group showed significantly better recovery than the control group [p=0.0001]. We concluded that memantine may decrease ischemic area in experimental cerebral ischemia in rats and it seems that memantine may be beneficial in cerebral ischemia

Dose dependent effect of memantine on long term potentiation in the CA 1 area of the hippocampus

Generally, NMDA receptor antagonists inhibit learning and long-term potentiation [LTP]. However, it has been suggested that direct tonic activation of NMDA receptors, in contrast to learning, may lead to an increase in synaptic "noise". Uncompetitive NMDA receptor antagonist memantine can paradoxically reverse deficits in learning and synaptic plasticity, and restore LTP impaired by tonic NMDA receptor activation. Adult rats weighed 200 to 250g were used in this in vivo study. Stimulating Schaffer collaterals field excitatory postsynaptic potentials [fEPSPs] were evoked in neurons of the CA1 area of the hippocampus. For induction of LTP, high frequency stimulation was applied to the path. Pre- and post-tetanic fEPSPs were recorded extracellularly in the anesthetized rats. Test groups were administered intraperitoneally with memantine [10 mg/kg or20 mg/kg] and the control animals received equal volumes of saline. Our results express that the drug has no effect on the baseline EPSPs. The tetanic stimulation induced a pronounced LTP in the control group lasting at least 2 hours. The animals treated with 10mg/kg of memantine also displayed a significant LTP; however, the potentiation was lower than the controls. The high frequency stimulation under administration of 20mg/kg of memantine failed to induce LTP in the fEPSPs. These findings point out a dose dependent attenuation of LTP by memantine. Comparison of the present data and those indicating the ability of memantine to restore LTP led us to conclude that, due to the activation level of the recording path, this moderate affinity NMDA receptor antagonist displays different effects on potentiation of hippocampal recordings