Brain distribution of hydrazine and its GABA elevating effect in rats

Area of Science:

• Neuroscience
• Pharmacology
• Analytical Chemistry

Background:

• Isoniazid (INH) is a primary drug for tuberculosis treatment.
• Hydrazine (Hz) is a known metabolite of INH.
• Gamma-aminobutyric acid (GABA) is a key inhibitory neurotransmitter in the brain.

Purpose of the Study:

• To quantify brain levels of hydrazine (Hz) and gamma-aminobutyric acid (GABA) after intravenous administration of INH and Hz.
• To compare the GABA-elevating effects of Hz and INH in the brain.

Main Methods:

• Intravenous administration of isoniazid (INH) and hydrazine (Hz) to subjects.
• Quantification of Hz and GABA in brain tissue using gas chromatograph-mass spectrometer (GC-MS).
• Utilized deuterium-labeled GABA (d2-GABA) and nitrogen-15 labeled Hz (15N-Hz) as internal standards for precise measurement.

Main Results:

• Both Hz and GABA were successfully detected in brain tissue following administration of either INH or Hz.
• Hydrazine (Hz) demonstrated a significantly higher effect on elevating brain GABA levels compared to isoniazid (INH).
• This pronounced GABA-elevating effect of Hz was observed even at a lower administered dose.

Conclusions:

• Intravenous administration of both INH and Hz leads to detectable levels of Hz and GABA in the brain.
• Hydrazine is a more potent agent for increasing brain GABA concentrations than its parent compound, isoniazid.
• These findings provide quantitative insights into the neurochemical effects of INH metabolism.