Solvent effects on the reactivity of fluorenyl nitrenium ion with DNA-like probes.

Laser Flash Photolysis (LFP) experiments carried out on 2-azidofluorene in aqueous systems generate 2-fluorenyl nitrenium ion (lambda(max) = 450 nm) which decays with first order rate constant and is quenched with 2'-deoxyguanosine originating an intermediate, namely the C8 adduct of 2-fluorenyl nitrenium ion, with bimolecular rate constant in the order of 1.3 x 10(9) M(-1) s(-1) in pure water. This intermediate very likely mimics the intermediate formed from carcinogens (i.

Contrasting loxapine to its isomer isoloxapine--the critical role of in vivo D2 blockade in determining atypicality.

Background: Loxapine is a typical antipsychotic while isoloxapine, its 8Cl-isomer, shows atypicality in some animal models. The basis for this difference is not well understood. The purpose of this study was to systematically compare the two drugs in in vitro and in vivo animal models, and to understand mechanisms underlying their differential typical/atypical profiles.

Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action.

Typical antipsychotics (haloperidol) give rise to severe motor side-effects while atypical antipsychotics like clozapine do not. Action at several neurotransmitter receptors have been implicated. To identify the critical mechanisms involved we synthesized an 8-C1 isomer of clozapine which showed an equivalent affinity to clozapine on multiple receptors (5-HT1A, 5-HT2, D1, D4, M1) but differed in having a 10-fold higher affinity at the dopamine D2/3 receptor.