The effects of pirlindole and dehydro-pirlindole on GABAA receptors and MAO-A activity were investigated in vitro. Pirlindole was inactive as a GABA antagonist. Dehydro-pirlindole exhibited partial and selective blockade of a subset of GABAA receptors with an EC50 of 12 microM and maximum reversal (delta Bopt) of 42%. Inhibition of rat brain and human placenta MAO-A by both compounds was much more potent (with IC50 range 0.3-0.005 microM). Their effects on MAO-A activity were partially reversible in vitro. In contrast to pirlindole, dehydro-pirlindole may act not only as MAO-A inhibitor but also as a clozapine-like selective GABAA receptor blocker, preferentially blocking a subset of GABAA receptors that are not sensitive to DMCM or Ro 5-4864.

Human plasma low density lipoproteins (LDL) contain a very high molecular weight protein termed apoB-100 (MC = 550,000). In many samples of LDL, minor components designated as apoB-74 (M, = 407,000) and apoB-26 (M, = 145,000) are present. It has been shown that they can arise as a result of proteolytic degradation of apoB-100. Our earlier studies demonstrated that the active forms of lipoprotein(a) (LP(a)) and apolipoprotein(a) (ape(a)) possess proteolytic activity. In the present study we investigated the possibility of apoB-100 degradation in the presence of activated ape(a). LDL were incubated with the puritkd ape(a) and analyzed by SDS-polyacrylamide gel electrophoresis. It was found that apoB is cleaved by ape(a) with formation of proteolytic fragments including B-74 and B-26. The physiological significance of apoB degradation under the action of ape(a) is considered.Lipoprotein(a); Apolipoprotein(a); Apolipoprotein B-100; Proteolytic degradation

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