During recent years many studies on the electroencephalogram (EEG) changes induced by almitrine-raubasine (Duxil) have been performed in elderly patients and in animals. This article gives an overview of three questions raised by their results. Is there a simple addition of the raubasine and almitrine effects when they are coadministered? Are the EEG effects of this treatment dependent on the patient's disease? To what extent could EEG studies provide some knowledge about the mechanism of action of almitrine-raubasine therapy? In adult (8 months) and aged (22 months) rats the EEG changes induced by the coadministration of almitrine and raubasine were significantly different from the addition of individual almitrine and raubasine EEG effects. In adult rats the coadministration induced slighter EEG changes than those predicted by the addition of almitrine and raubasine effects. In aged rats, the coadministration induced a decrease in delta-theta power not predictable from the effects of almitrine or raubasine. These results could be taken as an indication that some biological targets are common for the two drugs and that the coadministration results in pharmacological effects more complicated than a simple addition of raubasine and almitrine properties. After 3 weeks of treatment in aged healthy subjects, the coadministration induced an increase in the alpha and beta power with a slight decrease of delta and beta-1 powers. In patients with cognitive decline of probable degenerative origin, 3 months of theraphy with almitrine-raubasine was mainly associated with a decreased delta and theta power and a slight increase in high frequency components of the alpha band. The acute administration of the combination in elderly patients with cerebrovascular disease was followed by an important increase in the beta power, no change in the alpha power and a slight but significant increase in the theta power. All of these results suggest that the almitrine-raubasine combination enhances vigilance in healthy aged subjects (increase in alpha- and beta-1), arousal in patients with cognitive impairment of degenerative origin (decrease in theta), and the cerebral oxygen consumption in cerebrovascular disease (increase in beta-1 and beta-2). It appears that with this treatment and with other drugs (e.g., the benzodiazpines) the EEG changes induced by a drug are dependent on the pathology of the patient. As, of course, the pharmacological properties of the treatment are constant, these results suggest that EEG could be used to explore changes in the pathophysiology of the central nervous system associated with different diseases. Other studies were conducted in adult and aged rats to evaluate the almitrine and raubasine effects on the (noradrenalin) neurotransmission system. This was made by studying the interaction between clonidine and almitrine or raubasine or their association. Clonidine EEG effects were importantly attenuated when almitrine or raubasine or both were coadministered, and this occurred regardless of the age of the rat. Even if raubasine was generally more efficient than almitrine in attenuating the clonidine effects, both drugs showed remarkable similarities in their interactions with clonidine, and there were only a few cases in which almitrine and raubasine showed a net addition of their inhibitory actions on the clonidine EEG effects. The results suggest that almitrine and raubasine act on the noradrenaline system at close but not additive sites. Finally, the administration of almitrine-raubasine induces an increased noradrenergic transmission, which probably explain some of the pharmacological results in humans.
