PHARMACOLOGICAL STUDIES ON ALICYCLIC AMINES : (II) CENTRAL ACTIONS OF PIPERIDINE, PYRROLIDINE AND PIPERAZINE

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In the previous paper (1), it was reported that there are fundamental differences in pharmacological activities between alicyclic and aliphatic amines, and especially piperidine and pyrrolidine in alicyclic amines show pronounced synaptotropic actions similar to those of nicotine. Both of piperidine and pyrrolidine are normal constituents in the mammalian urine (2-5) and brain (6, 7). Furthermore, piperidine is normally present in human cerebrospinal fluid (8). When tritiated piperidine was given intravenously to the rabbit, it shows a definite distribution in the brain and particularly concentrates to the caudate nucleus, corpora quadrigemina and cortical region (9). However, nothing is known what kind of role piperidine plays in the brain. We have presumed that piperidine (and pyrrolidine also) might be an endogenous synaptotropic substance as Euler (10) and Abood (9) had stated before, serving some neural functions in the regulation of behaviour. In this respect, we have demonstrated that piperidine can be produced from pipecolic acid, an intermediate of lysine metabolism, by decarboxylase in the brain tissue (11). There has been an interest also in one of other alicyclic amines, piperazine, since it not only shows pharmacological activity such as emetic action (12) but also induces neuromuscular actions similar to those produced by inhibitory transmitters such as γ-aminobutyric acid (13, 14). In due consideration of the results described above, the central actions of alicyclic amines, especially those of piperidine, have been investigated in our laboratory. A number of drugs acting on the central nervous system (CNS) contain piperidine, pyrrolidine or piperazine groups in their chemical structures. It is well known that these alicyclic amino groups play essential or, at least, important role for the production of drug actions. Abood et al. (15-17) have reported the conspicuous psychotropic actions of piperidine- and piperazine-derivativand in connection with psychotropic properties of piperidine and piperazine. Nevertheless, little is known about the central actions of piperidine, pyrrolidine and piperazine per se. The present report is concerned with central actions especially neurophysiological and behavioural effects of piperidine, pyrrolidine and piperazine. Although central actions of morpholine have also been roughly studied, the amine was far weaker in its activities. So, the actions of morpholine are not described in this paper.
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PHARMACOLOGICAL STUDIES ON ALICYCLIC AMINES : (II) CENTRAL ACTIONS OF PIPERIDINE, PYRROLIDINE AND PIPERAZINE

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