Central dopaminergic and noradrenergic receptor blockade in a patient with neuroleptic malignant syndrome.

During treatment with clomipramine and haloperidol, a 54-year-old depressed woman exhibited a typical neuroleptic malignant syndrome (NMS). Among results of biologic tests performed at least 2 weeks after discontinuation of all psychotropic treatment, the absence of normal growth hormone response after both apomorphine and clonidine challenge tests and increased levels of cerebrospinal fluid homovanillic acid and urinary 3-methoxy-4-hydroxyphenylglycol suggest that NMS may be related to central dopaminergic and possible alpha-noradrenergic receptor blockade.

Effect of various antidepressant drugs on the spontaneous firing rate of locus coeruleus and dorsal raphe neurons of the rat.

The spontaneous firing rate of the noradrenergic neurons of the locus coeruleus and of the serotonergic neurons of the dorsal raphe was recorded with extracellular microelectrodes in chloral hydrate-anesthetized rats. A quantitative comparison of the effect of five tricyclic antidepressants, of tranylcypromine and of mianserin on the spontaneous activity of these two types of cells was performed. All drugs tested, except mianserin reduced the frequency of discharge of the noradrenergic neurons. Intravenous perfusion of the drugs allowed the doses required for inhibition of firing to 50% of the baseline rate (ID50) to be determined. Secondary aminated antidepressants (desipramine and nortriptyline) were more potent inhibitors than their tertiary aminated analogues (imipramine, chlorimipramine and amitriptyline). All drugs tested, except desipramine decreased the rate of firing of the serotonergic cells. In this case, the tertiary aminated antidepressants were much more potent than their secondary analogues. Mianserin was only active at very high doses. These results are in good agreement with the relative potencies of the tricyclic antidepressants for blocking the uptake of noradrenaline and serotonin into central and peripheral neurons.

Extrapyramidal signs following zimelidine overdose.

A 35-year-old woman with depression attempted suicide by taking an overdose of zimelidine (5 g), which was confirmed by zimelidine and norzimelidine plasma levels. Physical examination and repeat EKGs performed 2, 6, 9, and 12 hours later showed no alteration in her level of consciousness and only a slight increase in QT duration. However, the patient exhibited a distinct extrapyramidal syndrome, a finding consistent with animal data suggesting that zimelidine may possess some dopamine-receptor blockade properties.

Activity-dependent neurotrophic factor peptide (ADNF9) protects neurons against oxidative stress-induced death.

Activity-dependent neurotrophic factor (ADNF) and a 14-amino acid fragment of this peptide (sequence VLGGGSALLRSIPA) protect neurons from death associated with an array of toxic conditions, including amyloid beta-peptide, N-methyl-D-aspartate, tetrodotoxin, and the neurotoxic HIV envelope coat protein gp120. We report that an even smaller, nine-amino acid fragment (ADNF9) with the sequence SALLRSIPA potently protects cultured embryonic day 18 rat hippocampal neurons from oxidative injury and neuronal apoptosis induced by FeSO4 and trophic factor withdrawal. Among the characteristics of this protection are maintenance of mitochondrial function and a reduction in accumulation of intracellular reactive oxygen species.