Related Experiment Video

Updated: Jul 27, 2026

Generation of Local CA1 γ Oscillations by Tetanic Stimulation
08:02

Generation of Local CA1 γ Oscillations by Tetanic Stimulation

Published on: August 14, 2015

Antipsychotic drugs block IP3-dependent Ca(2+)-release from rat brain microsomes

S R Sczekan1, F Strumwasser

  • 1Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.

Biological Psychiatry
|September 15, 1996
PubMed

Insights

Antipsychotic drugs and calcium channel blockers directly inhibit IP3-induced calcium release in rat brain microsomes. This finding offers new insights into cellular calcium regulation relevant to bipolar affective disorder (BPAD).

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Cellular calcium dysregulation is implicated in diseases like bipolar affective disorder (BPAD) and malignant hyperthermia.
  • Plasma membrane calcium channel blockers (verapamil, nimodipine) show promise for BPAD treatment in lithium-responsive patients.

Purpose of the Study:

  • To investigate the effects of specific calcium channel blockers and antipsychotic drugs on inositol trisphosphate (IP3)-induced calcium release.
  • To determine if antipsychotic medications directly impact intracellular calcium release mechanisms.

Main Methods:

  • Experiments utilized Ca(2+)-loaded rat brain microsomes.
  • The study measured the inhibition of IP3-induced Ca(2+) release in the presence of various drugs.
  • Dose-dependent effects and EC50 values were determined for tested compounds.

Main Results:

  • Both calcium channel blockers (verapamil, nimodipine) and antipsychotic drugs (clozapine, fluspirilene, haloperidol) dose-dependently blocked IP3-induced Ca(2+) release.
  • Antipsychotics showed varying potencies, with fluspirilene (EC50=22 µM) being more potent than haloperidol (EC50=145 µM).
  • Anticonvulsants (carbamazepine, valproic acid) and haloperidol metabolites were largely ineffective.

Conclusions:

  • This research provides the first evidence that antipsychotic drugs directly inhibit IP3-induced Ca(2+) release from rat brain microsomes.
  • The findings suggest a direct molecular mechanism for how certain antipsychotics and calcium channel blockers may exert their therapeutic effects by modulating intracellular calcium signaling.

More Related Videos

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins09:07

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins

Published on: August 15, 2017

Dual Extracellular Recordings in the Mouse Hippocampus and Prefrontal Cortex04:44

Dual Extracellular Recordings in the Mouse Hippocampus and Prefrontal Cortex

Published on: February 16, 2024

Related Concept Videos

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium...
Psychosis and Antipsychotic Drugs: Overview01:28

Psychosis and Antipsychotic Drugs: Overview

The term "psychosis" refers to a spectrum of mental disorders characterized by abnormal thoughts, perceptions, and behaviors. It can manifest as mood disorders, dementia, delirium with psychotic features, substance-induced psychosis with psychotic features, brief psychotic disorder, delusional disorder, schizoaffective disorder, and schizophrenia. Among all these disorders, schizophrenia is the most common psychotic disorder, affecting 1% of the worldwide population. Psychotic symptoms in all...
Antipsychotic Drugs: Typical and Atypical Agents01:21

Antipsychotic Drugs: Typical and Atypical Agents

Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...
Antipsychotic Drugs: Therapeutic Uses and Side Effects01:21

Antipsychotic Drugs: Therapeutic Uses and Side Effects

Antipsychotic drugs primarily block dopamine and serotonin receptors and cholinergic, adrenergic, and histaminergic receptors, thereby reducing hallucinations and delusions in conditions like schizophrenia. However, they can trigger unwanted extrapyramidal effects such as dystonias, Parkinson-like symptoms, and tardive dyskinesia.
Despite these side effects, antipsychotics are used therapeutically for various purposes, including managing schizophrenia, preventing nausea and vomiting, curbing...
Antiepileptic Drugs: Calcium Channel Blockers01:17

Antiepileptic Drugs: Calcium Channel Blockers

Calcium channel blockers, a class of antiepileptic drugs, regulate the flow of calcium ions within neurons.
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...