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In severe status asthmaticus basic medical treatment often fails to improve the patient's condition. Mechanical ventilation in this situation is associated with a high incidence of serious complications. After the bronchodilating effect of moderate-dose magnesium sulfate in asthmatic patients had been demonstrated in previous studies we treated five mechanically ventilated patients with refractory status asthmaticus successfully with high dosages of MgSO4 IV (10-20 g within 1 h depending on the bronchodilating effect). MgSO4 resulted in a significant decrease of peak airway pressure (43.0 +/- 6.8 to 32.0 +/- 8.0 cmH2O) and inspiratory flow resistance (22.7 +/- 7.0 to 11.9 +/- 6.0 cmH2O.l-1.s-1) within 1 h. The resulting serum magnesium levels after one hour were up to threefold of the normal serum levels. Although a maintainance dose of 0.4 g/h had been administered continuously during the following 24 h serum magnesium decreased towards normal values within this time. The only relevant side-effect was a mild to moderate arterial hypotension in two of the five patients during the high dose administration period of MgSO4 which responded readily to dopamine treatment.

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Typical antipsychotic drugs, such as haloperidol and chlorpromazine, increase synthesis of the neuropeptide neurotensin (NT) in both the striatum and the nucleus accumbens, whereas atypical antipsychotic drugs, such as clozapine and olanzapine, do so only in the nucleus accumbens. By using in vivo microdialysis, we now report that acute administration of haloperidol, clozapine, or olanzapine failed to alter the release of NT in either the striatum or nucleus accumbens. In contrast, chronic administration of haloperidol for 21 days increased NT release in both the striatum and nucleus accumbens, whereas treatment for 21 days with the atypical antipsychotic drugs, clozapine or olanzapine, increased NT release selectively in the nucleus accumbens. These findings suggest that (i) increased NT mRNA expression and NT tissue concentrations are associated with increases in the extracellular f luid concentrations of the peptide and (ii) atypical antipsychotic drugs may exert their therapeutic effects and produce fewer side effects by virtue of their selectivity in limbic compared with striatal, target neurons.The tridecapeptide neurotensin (NT) first was isolated and characterized structurally in 1973 (1). It rapidly was shown to fulfill neurotransmitter criteria, including heterogenous regional brain distribution (in a variety of mammals, including humans), calcium-dependent and depolarization-induced release, localization in synaptic ventricles, electrophysiological actions on central neurons, and the presence of high affinity NT receptors. When injected directly into the central nervous system, NT produces a number of effects strikingly similar to antipsychotic drugs, particularly the so-called atypical antipsychotics. These effects include inhibition of avoidance but not of escape, responding in a discrete trial-conditioned avoidance paradigm, blockade of psychostimulant-induced locomotor hyperactivity, and reduced rates of intracranial electrical selfstimulation (2-4). Moreover, in several studies, cerebrospinal fluid (CSF) concentrations of NT have been shown to be reduced in drug-free schizophrenic patients when compared with controls. After antipsychotic drug treatment, CSF NT concentrations increase toward normal levels (5-8). Furthermore, the administration of antipsychotic drugs in laboratory animals has been shown repeatedly to alter central nervous system NT systems (9-12). In the rat, antipsychotic drug administration results in large increases in both NT tissue concentrations and in the expression of preproneurotensin mRNA in the basal ganglia (11,12). Of most interest, NT synthesis is altered differentially in the basal ganglia after the administration of typical vs. atypical antipsychotic drugs. Typical antipsychotics, such as haloperidol and chlorpromazine, increase NT mRNA expression and NT tissue concentrations in both the caudate nucleus and the nucleus accumbens, which are dopamine terminal regions for the nigroneostriatal and mesolimbic systems, respectively. In contrast, atypical antipsych...

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