ABSTRACT
The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN--a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four classical antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, and valproate) in the mouse maximal electroshock seizure (MES) model. The results indicate that WIN (10 mg/kg, i.p.) significantly enhanced the anticonvulsant action of carbamazepine, phenytoin, phenobarbital and valproate in the MES test in mice. WIN (5 mg/kg) potentiated the anticonvulsant action of carbamazepine and valproate, but not that of phenytoin or phenobarbital in the MES test in mice. However, WIN administered alone and in combination with carbamazepine, phenytoin, phenobarbital and valproate significantly reduced muscular strength in mice in the grip-strength test. In the passive avoidance task, WIN in combination with phenobarbital, phenytoin and valproate significantly impaired long-term memory in mice. In the chimney test, only the combinations of WIN with phenobarbital and valproate significantly impaired motor coordination in mice. In conclusion, WIN enhanced the anticonvulsant action of carbamazepine, phenytoin, phenobarbital and valproate in the MES test. However, the utmost caution is advised when combining WIN with classical antiepileptic drugs due to impairment of motor coordination and long-term memory and/or reduction of skeletal muscular strength that might appear during combined treatment.
Subject(s)
Anticonvulsants/administration & dosage , Benzoxazines/administration & dosage , Morpholines/administration & dosage , Naphthalenes/administration & dosage , Seizures/prevention & control , Animals , Avoidance Learning/drug effects , Benzoxazines/toxicity , Cannabinoid Receptor Agonists , Carbamazepine/administration & dosage , Drug Synergism , Electroshock , Male , Memory, Long-Term/drug effects , Mice , Morpholines/toxicity , Muscle Strength/drug effects , Naphthalenes/toxicity , Phenobarbital/administration & dosage , Phenytoin/administration & dosage , Psychomotor Performance/drug effects , Seizures/etiology , Valproic Acid/administration & dosageABSTRACT
The aim of the study was to fabricate a biodegradable bio-composite using only natural biological precursors for both composite components, i.e., for a support and for a filler. Bio-composites of biomorphous structure were prepared using monolithic blocks of yucca (Yucca flaccida) carbonised at 550°C as a stiff porous skeleton, and chitosan as a filler that coated the internal surface of the skeleton by a thin film. Highly porous supports and the resultant biomorphous composites were characterized by means of TGA, SEM, low-temperature physical adsorption of nitrogen, as well as electric and ultrasonic measurements. The resultant bio-composites were found to be very light materials with density of about 0.13g/cm3 and very porous (over 90%). They were found to be hierarchically ordered anisotropic structures with a stiff skeleton of dynamic elastic moduli up to 0.8GPa. The specific surface area was found to be 72m2/g giving a surface area of chitosan film equal to about 12m2 for a block sample of a volume of 2cm3. Covering porous support by thin film of chitosan resulted in the increase of electrical conductivity of the resultant composite.
