Haloperidol specificity

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

DA neurons in this nucleus, that not all the effects are elicited by the release of DA. Most neuroleptics block the inhibitory effects of applied DA but some, e.g. haloperidol, are less active against SN-evoked inhibition. Generally these studies lacked specific agonists and antagonists used microintophoresis which is not really quantitative and with extracellular recording gave little information on the state of polarisation of the neuron. 

The drug inhibition profile of (+)3H-SKF-10,047 binding is similar in many ways to that of (+)3H-3-PPP binding, but has some important differences. While pentazocine and SKF-10,047 are both potent inhibitors of (+)3H-SKF-10,047 binding, haloperidol and (+)3H-3-PPP inhibit only a portion of total specific (+)3H-SKF-... 

IC50 values for ( + )3-PPP and haloperidol against the portion of specific (+)3H-... 

With the introduction of chlorpromazine in 1952, there was a small revolution in psychiatry patients suffering from psychosis were able to be de-institutionalized. Chlorpromazine and other typical antipsychotics (e.g., haloperidol) demonstrate high in vitro binding affinities for the dopamine D2 receptor (D2). Specifically, their... 

Drew KL, O Connor WT, Kehr J, Ungerstedt U. 1990. Regional specific effects of clozapine and haloperidol on GABA and dopamine release in rat basal ganglia. Eur J Pharmacol 187(3) 385-397. 

Some first-generation agents, such as haloperidol, are rather specific for one subtype of dopamine receptor, D2. This suggests that some degree of both efficacy and side effects are associated with dopamine antagonism at this receptor. However, the situation is complex, as usual. There are five classes of dopamine receptors known Di through D5. To complicate matters further, several of these classes have subclasses. In total, there are at least 15 dopamine receptors. Which of these is important for relief of the symptoms of schizophrenia Which is responsible for movement disorders The answers to these questions are incomplete. We do have a few hints. 

There is another reason why medications exert multiple effects. For example, an antidepressant that very specifically promotes serotonin neurotransmission and has little or no interaction with other receptor types will still produce multiple effects. How can this be Remember that in different areas of the brain, a single neurotransmitter can assume very distinct roles. When an individual takes a medication that alters the activity of a particular neurotransmitter, it generally does so throughout the brain. Consequently, the dopamine receptor blocking effect of haloperidol (Haldol) reduces hallucinations and paranoia in one brain region but causes upper extremity stiffness through its action in another brain region. 

Drugs that are successful in treating the disease act as dopamine receptor blockers and are known as antipsychot-ics or neuroleptics (e.g. chlorpromazine, haloperidol). Antipsychotic drags reduce some of the symptoms, especially the delusions and hallucinations. A side-effect of the drugs is that they can result in symptoms similar to those seen in patients with Parkinson s disease. This is not surprising, since the hypothesis to explain Parkinson s disease is too low a concentration of dopamine in a specific area of the brain (see below). 

Patients in whom haloperidol is contraindicated can be treated by intramuscular injection of benzodiazepines, but these can cause respiratory depression or respiratory arrest if given in too high a dose, are contra-indicated in patients with preexisting respiratory depression, and have no specific anti-psychotic effect. 

C. Shiue, J.S. Fowler, A.P. Wolf, M. Watanabe, C.D. Arnett, Synthesis and specific activity determination of NCA F-labeled butyrophenone neuroleptics Benperidol, haloperidol, spiroperidol and pipamperone, J. Nucl. Med. 26 (1985) 181-186. 

Studies of the use of the specific serotonin-uptake inhibitors (SSRIs) to treat OCD suggest that, compared to non-tic-related OCD, tic-related OCD is less responsive to SSRI monotherapy (McDougle et al., 1993, 1994). Addition of a neuroleptic, such as haloperidol (McDougle et ah, 1994), risperidone (McDougle et al., 2000), or olanzapine (Bogetto et al., 2000), appears to be useful in improving treatment-resistant individuals response to a SSRI. It is unclear whether this pattern of treatment response is specifically associated with a comorbid tic disorder the pattern of obsessive compulsive symptoms characteristic of TS or yet some other predictors. 

D2 receptor, albeit with different specificity. Older examples of dopamine antagonists are chlorpromazine, haloperidol and many derivatives of these prototype compounds. Newer antipsychotic drugs such as risperidone, olanzapine and quetiapine have retained this mechanism of action, although no longer exclusively. 

Antipsychotics. Clear guidelines for measuring therapeutic serum concentrations of antipsychotics have not yet been established. There may, however, be specific situations in which they may be of value (e.g., monitoring of haloperidol [HPDL] levels might be useful in patients on concurrent carbamazepine therapy because the latter agent can substantially reduce serum HPDL concentrations). These issues are discussed in greater detail in the Pharmacokinetics/Plasma Level section in Chapter 5. 

Pimozide is FDA-labeled for Tourette s disorder and is particularly interesting in that it is a highly specific DA antagonist that may produce fewer adverse effects than haloperidol. In open studies with adequate doses, this agent has demonstrated efficacy for acute schizophrenia. Several double-blind trials comparing pimozide with other neuroleptics also found it to be an equally effective maintenance therapy ( 34, 35, 36, 37 and 38). We consider this agent to be as effective as the other standard agents, with the same, but perhaps less severe, side effects. 

Flaloperidol has documented efficacy in both the short-term and the long-term treatment of such patients (167). Specifically, haloperidol can reduce... 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

Aryltriazenes can also be decomposed by hydrogen fluoride in organic solution after extraction from their aqueous mother phase. In this case, hydrogen fluoride can be used in small excess but the nature of the solvent is crucial for example, tetrahydrofuran gives complex mixtures, dichloromethane promotes radical reactions (dimerizations, reductions) and acetic acid favors triazene decomposition before fluorination. Aromatic and haloaromatic compounds seem to be the best solvents.283 Such a technique, especially suited for the rapid introduction of an 18F atom, has been employed to produce [ 8F]haloperidol (3), the specific receptors of which have been localized in the brain by positron emission transaxial tomography.298... 

Subchronic oral administration of lithium causes a time-dependent increase in the substance P level in the striatum, which is prevented by coadministration of haloperidol. In PC 12 pheochromocytoma cells, lithium dramatically increases the intracellular levels of the neuropeptide neurotensin and the mRNA encoding it. An extensive overlap between specific and high-affinity neurotensin binding sites and dopamine perikarya and dendrites has been shown to occur in the mesocorticolimbic and nigrostriatal projection systems. Consistent with this observation are the results of observations showing that cocaine, an indirect sympathomimetic agent that enhances the extrapyramidal dopaminergic activity, increases dramatically the striatal content of neurotensin-like immunoreactivity. 

When making a choice of test situations, some investigators are biased by the effects of the tested substance in adulthood. Based on this knowledge, it is possible to formulate and test a specific hypothesis about aspects of brain and behavioral development that are expected to be affected. For instance, haloperidol can be expected to alter development of the dopamine system and motor activity, whereas clonidine can be expected to affect development of the catecholamine system and REM sleep. 

Rothblat DS, Schneider JS (1997) Regionally specific effects of haloperidol and clozapine on dopamine reuptake in the striatum. Neurosci Lett 228 119-22 Roy-Byrne PP (2005) The GABA-benzodiazepine receptor complex structure, function, and role in anxiety. J Clin Psychiatry 66 Suppl 2 14-20... 

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