Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Central Nervous System (CNS)
Neurodegeneration
Sensory system
Motor control
Mood Disorders
Other disorders
Muscular system
Joints
Metabolism
Cross-disciplinary subjects
Preclinical studies and opioids: role in crisis management in the United States Authors
D. Nieoczym, J. _uszczki, S. Czuczwar, P. Wlaz.
Lab
Maria Curie-Sk_odowska University, Institute of Biology, Department of Animal Physiology, Lublin, Poland.
Journal
Epilepsia
Abstract
PURPOSE: The goal of the present study was to evaluate the effects of sildenafil on the threshold for electrically induced seizures in mice. In addition, interactions between sildenafil and classical and second-generation antiepileptic drugs (AEDs), that is, carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), valproate (VPA), lamotrigine (LTG), topiramate (TPM), and oxcarbazepine (OXC) were evaluated. METHODS: Two electroconvulsive tests were used: maximal electroshock seizure threshold (MEST) and maximal electroshock seizure (MES) tests in mice. Acute adverse effects of the studied combinations were investigated in the chimney test, step-through passive avoidance task, and grip-strength test. Total brain and free plasma concentrations of AEDs were also determined. RESULTS: Sildenafil raised the threshold for electroconvulsions in a dose-dependent manner. It also increased the anticonvulsant activity of CBZ, VPA, and TPM in the MES test, whereas the activity of the remaining AEDs was not significantly changed. Sildenafil increased total brain and free (protein unbound) plasma CBZ concentrations and total brain VPA concentration. Neither sildenafil nor its coadministration with the studied AEDs affected motor coordination and long-term memory in mice. Interestingly, sildenafil dose-dependently enhanced the skeletal muscle strength in mice, although combinations of sildenafil with AEDs were ineffective in this respect. CONCLUSIONS: Sildenafil significantly raised the threshold for electroconvulsions in mice without any impairment of motor performance and long-term memory, but it enhanced muscle strength. Treatment of patients on CBZ or VPA with sildenafil may not be recommended due to pharmacokinetic interactions. Coadministration of sildenafil with other AEDs, especially with TPM, seems to be a reasonable choice.
BIOSEB Instruments Used:
Grip strength test (BIO-GS3)
