Science News
from research organizations

Dopamine receptor blockade seen as cause for antipsychotic drug side-effects

Targeted pharmaceutical approach for eliminating this problem

Date:
July 6, 2016
Source:
University of California - Irvine
Summary:
Scientists have discovered the key cellular mechanism that underlies the antipsychotic-induced parkinsonism -- which includes involuntary movements, tremors and other severe physical conditions. These studies present evidence that will stimulate a targeted approach for the design of novel antipsychotics without side-effects.
Share:
FULL STORY

Since their development in the 1950s, antipsychotic drugs have been widely used to treat psychoses and neuropsychiatric disorders like schizophrenia. A debilitating side-effect of these drugs called parkinsonism limits their efficacy.

University of California, Irvine scientists led by Emiliana Borrelli and colleagues have discovered the key cellular mechanism that underlies the antipsychotic-induced parkinsonism -- which includes involuntary movements, tremors and other severe physical conditions. These studies present evidence that will stimulate a targeted approach for the design of novel antipsychotics without side-effects.

In the journal Neuron, the researchers report that antipsychotics side-effects are due to blockade of the dopamine D2 receptor in a specialized type of neurons in the striatum, called interneurons. Blockade of D2 receptor in these neurons increases neurotransmitter signaling (acetylcholine) above threshold on neighbor neurons leading to motor abnormalities in rodents (catalepsy) and in humans (parkinsonism). Catalepsy is marked by severe muscular rigidity and fixity of posture regardless of external stimuli. Indeed, in mouse studies, the Borrelli team discovered that removing D2 receptors in nerve cells (cholinergic interneurons) did not result in catalepsy in the mice upon antipsychotic treatment.

Borrelli said the importance of this study is twofold. It clarifies a long-waited mechanism that allows to explain the motor side-effects of antipsychotic drugs and will help future design of drugs deprived of nasty side-effects. It also generates important information for combined therapies (using drugs that block D2 but also acetylcholine receptors) that should be used to improve the life of people treated for debilitating psychiatric disorders.


Story Source:

Materials provided by University of California - Irvine. Note: Content may be edited for style and length.


Journal Reference:

  1. Geetika Kharkwal, Karen Brami-Cherrier, José E. Lizardi-Ortiz, Alexandra B. Nelson, Maria Ramos, Daniel Del Barrio, David Sulzer, Anatol C. Kreitzer, Emiliana Borrelli. Parkinsonism Driven by Antipsychotics Originates from Dopaminergic Control of Striatal Cholinergic Interneurons. Neuron, 2016; 91 (1): 67 DOI: 10.1016/j.neuron.2016.06.014

Cite This Page:

University of California - Irvine. "Dopamine receptor blockade seen as cause for antipsychotic drug side-effects: Targeted pharmaceutical approach for eliminating this problem." ScienceDaily. ScienceDaily, 6 July 2016. <www.sciencedaily.com/releases/2016/07/160706174359.htm>.
University of California - Irvine. (2016, July 6). Dopamine receptor blockade seen as cause for antipsychotic drug side-effects: Targeted pharmaceutical approach for eliminating this problem. ScienceDaily. Retrieved May 24, 2017 from www.sciencedaily.com/releases/2016/07/160706174359.htm
University of California - Irvine. "Dopamine receptor blockade seen as cause for antipsychotic drug side-effects: Targeted pharmaceutical approach for eliminating this problem." ScienceDaily. www.sciencedaily.com/releases/2016/07/160706174359.htm (accessed May 24, 2017).

RELATED STORIES