Donepezil, an acetylcholinesterase inhibitor, induces only moderate symptomatic effects on memory in Alzheimer's disease patients. An alternative strategy for treatment of cognitive symptoms could be to act simultaneously on both histaminergic and cholinergic pathways, to create a synergistic effect. To that aim, 14 month old C57/Bl6 mice were administered per oesophagy during nine consecutive days with Donepezil (at 0.1 and 0.3 mg/kg) and S 38093 (at 0.1, 0.3, and 1.0 mg/kg), a H3 histaminergic antagonist developed by Servier, alone or in combination and tested for memory in a contextual memory task that modelized the age-induced memory dysfunction. The present study shows that the combination of Donepezil and S 38093 induced a dose-dependent synergistic memory-enhancing effect in middle-aged mice with a statistically higher size of effect never obtained with compounds alone and without any pharmacokinetic interaction between both compounds. We demonstrated that the memory-enhancing effect of the S 38093 and Donepezil combination is mediated by its action on the septo-hippocampal circuitry, since it canceled out the reduction of CREB phosphorylation (pCREB) observed in these brain areas in vehicle-treated middle-aged animals. Overall, the effects of drug combinations on pCREB in the hippocampus indicate that the synergistic promnesiant effects of the combination on memory performance in middle-aged mice stem primarily from an enhancement of neural activity in the septo-hippocampal system.
Title: Additional studies with new insecticides as residual spray in buildings naturally infested with anopheles quadrimaculatus Gahan JB, Wilson HG, Smith CN Ref: Bulletin of the World Health Organization, 32:169, 1965 : PubMed
Because some species of Anopheles mosquitos have been developing resistance to DDT and dieldrin, field studies have been conducted to evaluate the effectiveness of recently developed insecticides as residual sprays in buildings naturally infested with adults of Anopheles quadrimaculatus. As a deposit at 2 g/m(2), o-isopropoxyphenyl methylcarbamate remained highly effective for more than one year. This compound and 6-chloro-3,4-xylyl methylcarbamate were still producing excellent control 11-12 weeks after application at 1 g/m(2). Other highly effective materials were m-isopropylphenyl methylcarbamate and 4-(methylthio)-3,5-xylyl methylcarbamate at 2 g/m(2). At the present time, o-isopropoxyphenyl methylcarbamate appears to offer the best prospects for use in residual spray programmes because it has long residual action, affects mosquitos rapidly, has only a slight odour and appears to be safe to use if spraymen take reasonable precautions.
Title: STUDIES ON THE INHERITANCE OF CARBAMATE-RESISTANCE IN THE HOUSEFLY (MUSCA DOMESTICA L.) Georghiou GP, Garber MJ Ref: Bulletin of the World Health Organization, 32:181, 1965 : PubMed
In view of the increasing importance of carbamic acid esters in insect control, the authors have conducted studies on the inheritance of carbamate-resistance in the housefly Resistance to Isolan (1-isopropyl-3-methyl-5-pyrazolyl dimethylcarbamate) in carbamate-selected strains is inherited as a partially dominant major single factor, without sex linkage or appreciable cytoplasmic influence. Inclusion of piperonyl butoxide as a synergist with Sevin (1-naphthyl methylcarbamate), Zectran (4-dimethylamino-3,5-xylyl methylcarbamate), or m-isopropylphenyl methylcarbamate also produced evidence of monofactorial inheritance.In contrast, resistance to Isolan and to a combination of Sevin and piperonyl butoxide in a ronnel-selected strain is inherited in a pattern suggestive of a polygenic system.The results obtained are discussed in the light of previously established data on the rate of development, stability and regression of carbamate-resistance.
