Acute Octodrine (DMHA) Exposure Disrupts Cardiac Function, Locomotor Activity, and Neuronal Activity-Responsive Transcription in Zebrafish Larvae.
4 affiliations
- 1Laboratory of Environmental Mutagenesis, Department of Biophysics and Biometry, Rio de Janeiro State University (UERJ), Rio de Janeiro 20551-030, RJ, Brazil.
- 2Integrated Laboratory of Environmental Mutagenesis, Department of Genetics and Molecular Biology, Federal University of Rio de Janeiro State (UNIRIO), Rio de Janeiro 20211-010, RJ, Brazil.
- 3Institute for Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona, 18, 08034 Barcelona, Spain.
- 4Research and Development Center (CID-CSIC), Jordi Girona, 18, 08034 Barcelona, Spain.
Abstract
Octodrine (2-amino-6-methylheptane; DMHA) is a sympathomimetic stimulant detected in sports-performance and weight-loss supplements despite limited toxicological characterization and regulatory concerns. Here, we used 7-day-post-fertilization zebrafish larvae to characterize the acute cardiac, neurobehavioral, and transcriptional effects of octodrine after 2 h of exposure. Cardiac responses were biphasic: 5 µM octodrine significantly increased atrial and ventricular rates, whereas concentrations ≥ 150 µM produced progressive cardiac depression and higher concentrations disrupted atrioventricular conduction. At 450 µM, all larvae showed complete absence of detectable cardiac activity; mortality was not independently assessed. Modelling of the inhibitory phase yielded IC₅₀ values of 195.6 µM for atrial rate and 188.8 µM for ventricular rate. At substantially lower concentrations, octodrine significantly reduced spontaneous locomotor activity. After Holm correction across all 24 planned time-by-treatment comparisons, a transient effect remained detectable at 50 nM, with more sustained hypoactivity at 0.5 and 5 µM across most of the 2 h exposure period. At the transcriptional level, 3.5 µM octodrine significantly reduced fosab and egr1 expression, whereas fkbp5 was induced at selected concentrations; npas4a showed a significant overall treatment effect but no dose-specific comparison remained significant after blocked analysis and multiplicity correction. nr4a1 was significantly downregulated at 350 µM, whereas th1 and kcnh2a expression was not significantly altered. Together, these findings show that neurobehavioral/transcriptional responses and pronounced cardiac dysfunction occurred over different concentration ranges under the conditions tested. The results provide an initial in vivo hazard characterization of octodrine and support further investigation of its neuropharmacological mechanisms, internal exposure, and cardiovascular safety.
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BibTeX
@article{carraodantas2026acute,
title = {{Acute Octodrine (DMHA) Exposure Disrupts Cardiac Function, Locomotor Activity, and Neuronal Activity-Responsive Transcription in Zebrafish Larvae.}},
author = {Eduardo Kennedy Carrão-Dantas and Ouwais Aljabasini and Eva Prats and Israel Felzenszwalb and Carlos Fernando Araujo-Lima and Demetrio Raldúa},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198560},
url = {https://europepmc.org/article/MED/42883807},
note = {CC BY},
}
RIS
TY - JOUR
TI - Acute Octodrine (DMHA) Exposure Disrupts Cardiac Function, Locomotor Activity, and Neuronal Activity-Responsive Transcription in Zebrafish Larvae.
AU - Eduardo Kennedy Carrão-Dantas
AU - Ouwais Aljabasini
AU - Eva Prats
AU - Israel Felzenszwalb
AU - Carlos Fernando Araujo-Lima
AU - Demetrio Raldúa
PY - 2026
DA - 2026/09/24
JO - International journal of molecular sciences
DO - 10.3390/ijms27198560
UR - https://europepmc.org/article/MED/42883807
AB - Octodrine (2-amino-6-methylheptane; DMHA) is a sympathomimetic stimulant detected in sports-performance and weight-loss supplements despite limited toxicological characterization and regulatory concerns. Here, we used 7-day-post-fertilization zebrafish larvae to characterize the acute cardiac, neurobehavioral, and transcriptional effects of octodrine after 2 h of exposure. Cardiac responses were biphasic: 5 µM octodrine significantly increased atrial and ventricular rates, whereas concentrations ≥ 150 µM produced progressive cardiac depression and higher concentrations disrupted atrioventricular conduction. At 450 µM, all larvae showed complete absence of detectable cardiac activity; mortality was not independently assessed. Modelling of the inhibitory phase yielded IC₅₀ values of 195.6 µM for atrial rate and 188.8 µM for ventricular rate. At substantially lower concentrations, octodrine significantly reduced spontaneous locomotor activity. After Holm correction across all 24 planned time-by-treatment comparisons, a transient effect remained detectable at 50 nM, with more sustained hypoactivity at 0.5 and 5 µM across most of the 2 h exposure period. At the transcriptional level, 3.5 µM octodrine significantly reduced fosab and egr1 expression, whereas fkbp5 was induced at selected concentrations; npas4a showed a significant overall treatment effect but no dose-specific comparison remained significant after blocked analysis and multiplicity correction. nr4a1 was significantly downregulated at 350 µM, whereas th1 and kcnh2a expression was not significantly altered. Together, these findings show that neurobehavioral/transcriptional responses and pronounced cardiac dysfunction occurred over different concentration ranges under the conditions tested. The results provide an initial in vivo hazard characterization of octodrine and support further investigation of its neuropharmacological mechanisms, internal exposure, and cardiovascular safety.
SN - 1422-0067
ER -