The relationship between properties of antipsychotic drugs and cataract formation

A. Kamei, Y. Mizumoto, M. Takehana

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

It has been reported that antipsychotic drugs such as phenothiazine derivatives, dibenzyl derivatives and others with calmodulin antagonism induce cataracts, which are generically called phenothiazine-induced cataracts. In the ophthalmologic field, the mechanism of cataractogenesis by such drugs is a problem urgently requiring a solution. This paper reports the relationship between the properties of such drugs and cataract formation. In this experiment, phenothiazine derivatives (chlorpromazine, trifluoperazine, prochlorperazine and perphenazine), dibenzyl derivatives (imipramine and amitriptyline), and other drugs (cyproheptadine and calmidazolium) were investigated. As a result, it was clarified that phenothiazine derivatives and calmidazolium have high lipophilicity, strong inhibition activity against phosphodiesterase, and a large permeability constant, and that those drugs induce high levels of Ca2+ accumulation in the lens. It was also revealed that those drugs were distributed only at the peripheral region of the lens after they had penetrated into the lens. From these findings, we inferred that the cataract formation may be caused by lens protein aggregation followed by the inactivation of calmodulin-dependent Ca-ATPase and subsequent Ca2+ accumulation in the lens. Furthermore, we have been convinced that it is necessary to lower at least the lipophilicity of these drugs to suppress the side effect of antipsychotic drugs inducing cataractic formation.

Original languageEnglish
Pages (from-to)237-242
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume17
Issue number2
Publication statusPublished - 1994

Fingerprint

Cataract
Antipsychotic Agents
Lenses
calmidazolium
Pharmaceutical Preparations
Calmodulin
Prochlorperazine
Perphenazine
Cyproheptadine
Trifluoperazine
Crystallins
Amitriptyline
Calcium-Transporting ATPases
Imipramine
Chlorpromazine
Phosphoric Diester Hydrolases
Drug-Related Side Effects and Adverse Reactions
Permeability
phenothiazine

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

The relationship between properties of antipsychotic drugs and cataract formation. / Kamei, A.; Mizumoto, Y.; Takehana, M.

In: Biological and Pharmaceutical Bulletin, Vol. 17, No. 2, 1994, p. 237-242.

Research output: Contribution to journalArticle

Kamei, A. ; Mizumoto, Y. ; Takehana, M. / The relationship between properties of antipsychotic drugs and cataract formation. In: Biological and Pharmaceutical Bulletin. 1994 ; Vol. 17, No. 2. pp. 237-242.
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