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Multimodal Photoswitchable Modulation of Insect Glutamatergic Transmission by Quaternary Ammonium Azobenzenes
Irina Fedorova1, Denis Tikhonov1, Maxim Nikolaev1
1I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, Thorez pr.44, 194223 Saint-Petersburg, Russia.
ACS Omega
|February 23, 2026
Summary
Photochromic channel blockers show varied effects on insect neuromuscular junctions. Even similar structures like QAQ, DENAQ, and AAQ exhibit distinct actions, highlighting the need for mechanism-specific drug development.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Photopharmacology offers precise control over biological processes.
- Azobenzene quaternary ammonium derivatives are effective in vertebrates but unstudied in insects.
Purpose of the Study:
- To investigate the effects of photomodulated channel blockers (QAQ, DENAQ, AAQ) on synaptic transmission in *Calliphora vicina* larvae.
- To compare the actions of structurally similar compounds and their light-dependent modulation.
Main Methods:
- Electrophysiological recordings at the neuromuscular junction of *Calliphora vicina* larvae.
- Application of QAQ, DENAQ, and AAQ at micromolar concentrations.
- Photoconversion between trans- and cis-isomers to assess light-dependent effects.
Main Results:
- QAQ inhibited excitatory postsynaptic currents by blocking glutamate receptors.
- DENAQ potentiated synaptic transmission by likely blocking presynaptic potassium channels, enhancing nerve excitability.
- AAQ exhibited a combined mechanism of action.
Conclusions:
- Structurally similar photopharmacological compounds can have diverse targets and mechanisms of action.
- Insect ion channels show evolutionary conservativity in their interaction with these blockers.
- Careful analysis of molecular mechanisms is crucial for the rational design of photochromic drugs.
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