Novel monoacetoneglucose derivatives with calcium antagonist activity.

Ethers and thioethers of monosaccharides have been synthesised which show potent toxicity to mouse (LD50 > or = 4 g.kg-1 O.W. and 0.2 to 1.5 g.kg-1 I.P.W.). A study of calcium antagonist activity for the full series of compounds indicated that the activity was similar for both O- and S- ethers and maximum activities were observed for monoacetoneglucose ethers possessing carbon chain close to 8 carbons.

[Effect of the nature of the heteroatom of a monosaccharide derivative on its inhibitory action in relation to P-type calcium channels expressed in the Xenopus oocyte]. / Influence de la nature de l'hétéroatome d'un dérivé monosaccharidique sur son action inhibitrice vis à vis de canaux calciques apparentés au type P exprimés dans l'ovocyte de Xenopus.

Our results demonstrate that saccharidic derivatives obtained by adding a C8 alkyl group through various heteroatomes (O, N or S) to a monoacetonide residue possess an inhibitory effect towards putative P-type calcium channels expressed in Xenopus oocytes. These derivatives partially and reversibly inhibit the activity these channels without changing their electrophysiological properties. Nevertheless, the derivative containing the heteroatome N also affects the fast and tetrodotoxin-sensitive sodium channel activity. Thus, only ether and thioether compounds (heteroatome O or S) can be selected for their inhibitory effect on P-type apparented calcium channels.

[The inhibitory action of a saccharide derivative on a calcium channel in the oocyte of Xenopus]. / Mise en évidence de l'action inhibitrice d'un dérivé saccharidique sur le canal calcique de l'ovocyte de Xénope.

Endogenous calcium channels of Xenopus oocyte membrane do not fit with pharmacological classification of calcium channels. The present study demonstrates that the saccharidic derivate, OC8-MAGlu-MAGlu, has potent inhibitory effect on this channel activity.

[Effects of the monosaccharide derivative 8RN-DAGal on the putative P-type calcium channel expressed in Xenopus oocytes]. / Effets du dérivé monosaccharidique 8RN-DAGal sur un courant calcique apparenté au type P exprimé dans l'ovocyte de Xénope.

P-type calcium channels are expressed in Xenopus oocytes after injection of rat cerebellar mRNA. The FTX and omega-Aga-IVa toxins extracted from Agelenopsis aperta venom are known to inhibit the activity of this channel. The present results demonstrate that 8RN-DAGal is also a antagonist of P-type calcium channels. The inhibition of the current, obtained with Ba2+, as charge carrier, is voltage dependent.