Neuroleptic drugs in the human brain

  title={Neuroleptic drugs in the human brain},
  author={Johannes Kornhuber and Jens Wiltfang and Peter Franz Riederer and Stefan Bleich},
  journal={European Archives of Psychiatry and Clinical Neuroscience},
After discontinuation of neuroleptic agents, their effects are still present for a long time. The exact underlaying mechanisms are still unclear. In two previous studies we measured the concentrations and region-specific distribution of haloperidol (Kornhuber et al. 1999) and levomepromazine (Kornhuber et al. 2006) in postmortem human brain tissues. The aim of the present paper is to compare the results of these two studies. Even after short-term treatment, haloperidol and levomepromazine… 
[The neurotoxicity of pyridinium metabolites of haloperidol].
Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such
Actions of psychotropic drugs beyond their primary targets at the synaptic cleft
This special issue contains five publications, each dealing with mechanisms of psychotropic drugs beyond the primary target binding sites, and the importance of P-gp for understanding drug–drug interactions.
Postmortem Quetiapine Reference Concentrations in Brain and Blood.
The brain concentrations of quetiapine observed in cases, where quetuapine was unrelated to death, may serve as a reference, when evaluating postmortem cases with no blood available, and give an indication of likely toxic concentrations.
Effect of herbal and nutritional products on the central nervous system effects of haloperidol: a systematic review
It is advised to monitor the potential risk of interactions between haloperidol and co-administrated HNPs in clinical practice, and consider factors such as modulations on oxidative stress and dopaminergic pathway were proposed.
Interaction of antidepressant and antipsychotic drugs with the human organic cation transporters hOCT1, hOCT2 and hOCT3
Under the assumption of a tenfold accumulation in the brain, bupropion, nefazodone and clozapine may notably inhibit the corresponding hOCTs and it remains to be shown whether such a direct inhibition plays a role in the clinical effects of these three drugs.
Differential effects of typical and atypical antipsychotics on astroglial cells in vitro
Novel Pharmacological Action of Clozapine at D2 Dopamine Receptors
It is shown that treatment with all APDs upregulates cell-surface expression of D2-dopamine receptors (D2R), relative to that produced by clozapine, and that APD upregulation of surface D2R is a consequence of direct receptor binding, suggesting that APDs act intracellularly as chemical chaperones to stabilize a conformation of D 2R with enhanced detergent solubility and transport to the cell surface.


Persistence of haloperidol in human brain tissue.
Haloperidol concentrations in the human brain tissue were 10-30 times higher than optimal serum concentrations used in the treatment of schizophrenia, and appeared to be homogeneously distributed across different brain areas within a single patient.
Region specific distribution of levomepromazine in the human brain
Levomepromazine shows a region-specific distribution in the human brain with highest values in the basal ganglia, which might be the consequence of low expression of the metabolic enzyme Cyp2D6 in the basement ganglia of neuroleptic patients.
Slow accumulation of psychotropic substances in the human brain. Relationship to therapeutic latency of neuroleptic and antidepressant drugs?
The mean daily oral dose of amantadine is low compared to the high storage capacity of brain and other tissues thus explaining the slow accumulation, which is likely for many antidepressant and neuroleptic drugs and has been directly demonstrated for fluoxetine.
Neurometabolic and behavioural effects of haloperidol in relation to drug levels in serum and brain
A good correlation was found between the haloperidol concentration in the brain on the one hand and its effects on behaviour, on serum prolactin values and on Dopa formation on the other.
Prolonged pharmacologic activity of neuroleptic drugs.
An experiment in which moderate single doses of haloperidol were administered to rats and found that the behavioral response to the dopamine agonist apomorphine was reduced significantly for at least one month showed a lack of concordance between dopamine D 2 receptor occupancy in the brains of schizophrenics and plasma haloperIDol levels following the withdrawal of the drug.
Differences between antipsychotic drugs in persistence of brain levels and behavioral effects
Findings, indicating marked differences in clearance and recovery times after dosing with butyrophenones and phenothiazines, have clear implications for studies of the effects of neuroleptic drugs in rats.
Blood to brain distribution of neuroleptics
Therapeutic brain concentration of the NMDA receptor antagonist amantadine
Drug distribution between blood and brain as a determinant of antipsychotic drug effects
Distribution of clozapine and desmethylclozapine between blood and brain in rats