In the search for compounds active against human immunodeficiency virus (HIV), we have found that members of a novel series of tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepine-2(1H)-one and -thione (TIBO) derivatives inhibit the replication of HIV-1, the main aetiological agent of AIDS, but not of HIV-2, or of any other DNA or RNA viruses. In five cell systems, HIV-1 is inhibited by TIBO derivatives in nanomolar amounts, which are 10(4)-10(5) times lower than the cytotoxic concentration. The unprecedented specificity of these compounds may be due to an interaction with a reverse transcriptase-associated process. By contrast, AZT (3'-azido-2',3'-dideoxythymidine), which is used for the treatment of AIDS, and DDC (2',3'-dideoxycytidine) and DDI (2',3'-dideoxyinosine), whose clinical application is being assessed, inhibit both HIV-1 and HIV-2 at concentrations that, depending on the cell systems, are 2 to 4 orders of magnitude below their cytotoxic concentration. TIBO-derivatives are new chemicals unrelated to any other antiviral agents. We believe that they are the most specific and potent inhibitors of HIV-1 replication studied so far.

Our chemical and pharmacological experimental programme8'9 in the field of substituted piperidines led to the discovery that 4-(4-hydroxy-4-phenylpiperidino)butyrophenone (I: L = R = H) was a powerful CNS depressant in various species. This unexpected result led us to investigate the CNS depressant properties of a new series of over 500 related basic ketones. The relevant chemical and pharmacological results obtained with these compounds will be presented and discussed in this series of papers.The purpose of this paper is to describe a convenient method of synthesis and some physicochemical properties, as well as some relevant CNS depressant properties in mice of a selected group of

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Oxatomide is a new potent inhibitor of anaphylactic and allergic reactions. After oral administration, the compound both inhibits the release of endogenous histamine and prevents the effects of exogensous histamine, at comparable doses. The combination of these effects appears to be the basis of the effectiveness of oxatomide in allergic reactions and may lead to clinical application different from classical antihistaminics and from cromoglycate.

Rats that had received 3% alcohol, 0.01% cocaine, or 0.002% fentanyl as the only beverage over 10 days showed marked preference for the drug solution when water was made available as a second fluid in a separate bottle. Treatment with low doses of ritanserin, a specific central serotonin 5-HT2 antagonist, rapidly reversed drug preference without changing total fluid intake. Quantitatively, the reduction in drug consumption was greater for alcohol than for cocaine and greater for cocaine than for fentanyl. This is probably related to differences in the reinforcing potential of the three drugs.