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Updated: Aug 15, 2026

Metabolic Profiling to Determine Bactericidal or Bacteriostatic Effects of New Natural Products using Isothermal Microcalorimetry
Published on: October 29, 2020
Effect of some psychotropic drugs and a barbiturate on mycoplasmas
1Mycoplasma Laboratory, Statens Seruminstitut, DK-2300, Copenhagen, Denmark.
Abstract:
The inhibitory effect of selected membrane stabilisers on Mycoplasma pneumoniae, M. hominis and Ureaplasma urealyticum was investigated in vitro. The phenothiazine chlorpromazine (CPZ) and the barbiturate thiopental (Leopental(R)) as well as the stereo-isomeric thioxanthene derivatives; cis(Z)-clopenthixol (Zu-clopenthixol(R))/ trans (E)-clopenthixol and cis (Z)-chlorprothixen (Truxal(R))/trans(E)-chlorprothixen, all have antimycoplasmal effect in the range 3.9-312 mg/l, measured as growth inhibition. It was also demonstrated that the enzymatic functions of the different mycoplasma strains, such as breakdown of glucose, arginine and urea, were abolished by concentrations of CPZ that were sufficiently low to allow multiplication of the organisms. A similar effect was obtained with Leopental(R) although the mycoplasmas were generally only half as sensitive to this drug. Also M. gallisepticum and Acholeplasma laidlawii were inhibited by CPZ and Thiopental. The four thioxanthenes were all inhibitory to mycoplasmal growth and the effect was independent of their stereo-isomeric configuration. The clopenthixol stereoisomers, but not the chlorprothixene isomers, inhibited colour change at concentrations lower than those which inhibited growth. While enzyme activity may continue for some time in vitro when classic antibiotics have inhibited mycoplasmal growth, the reverse effect was observed with phenothiazines and thioxanthenes. The membrane stabilisers may be useful tools in the investigation of microbiological activity on the mycoplasma membrane. From these drugs, new 'antibiotics' might be developed with another action than that of the known antimycoplasmal drugs.
Insights
Selected membrane stabilizers, including chlorpromazine (CPZ) and thiopental, show antimycoplasmal effects against various Mycoplasma species. These compounds inhibit mycoplasma growth and enzymatic functions, suggesting potential for new antibiotic development.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Mycoplasma species are significant human pathogens.
- Current treatments for mycoplasma infections have limitations.
- Membrane stabilizers are not typically considered antimicrobials.
Purpose of the Study:
- To investigate the in vitro inhibitory effects of selected membrane stabilizers on pathogenic Mycoplasma species.
- To evaluate the impact of these compounds on mycoplasma growth and enzymatic functions.
- To explore the potential of membrane stabilizers as a basis for novel antimicrobial drug development.
Main Methods:
- In vitro susceptibility testing of Mycoplasma pneumoniae, M. hominis, Ureaplasma urealyticum, M. gallisepticum, and Acholeplasma laidlawii.
- Assessing growth inhibition and enzymatic activity (glucose, arginine, urea breakdown) in the presence of chlorpromazine (CPZ), thiopental, and thioxanthene derivatives.
- Comparing the effects of different stereoisomers of thioxanthene derivatives.
Main Results:
- Chlorpromazine (CPZ), thiopental, and four thioxanthene derivatives demonstrated antimycoplasmal activity against all tested strains, with effective concentrations ranging from 3.9-312 mg/l.
- CPZ and thiopental inhibited mycoplasma enzymatic functions at concentrations lower than those inhibiting growth.
- Thioxanthene derivatives showed growth inhibition independent of their stereoisomeric configuration, with clopenthixol isomers also affecting color change at lower concentrations than growth inhibition.
Conclusions:
- Membrane stabilizers like phenothiazines and thioxanthenes possess significant antimycoplasmal activity.
- These compounds uniquely inhibit mycoplasma enzymatic functions at sub-growth-inhibitory concentrations.
- Membrane stabilizers represent promising candidates for developing novel antimycoplasmal agents with unique mechanisms of action.
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