4-Methyloctanoic acid

4-Methyloctanoic acid is an endogenous branched-chain medium-chain fatty acid and a negative regulator of the cAMP/PKA signaling pathway. 4-Methyloctanoic acid exerts antiepileptic effects by inhibiting epileptiform discharges and terminating behavioral and electroencephalographic seizures. 4-Methyloctanoic acid has neuroprotective effects; its polar metabolites can cross the blood-brain barrier, repair presynaptic release defects, improve motor function and alleviate neuromuscular degeneration in ALS models. 4-Methyloctanoic acid regulates phosphatidylinositol metabolism, reduces PIP/PIP₂ levels and increases inositol levels. 4-Methyloctanoic acid can be used in studies related to epilepsy and amyotrophic lateral sclerosis^{[1][2][3][4][5][6][7]}. In Vitro:4-Methyloctanoic acid (1 mM; 40 minutes) potently suppresses PTZ-induced epileptiform burst discharge frequency in combined entorhinal cortex-hippocampal slices, reducing activity to 49.14% of baseline^[1].
4-Methyloctanoic acid (1 mM; 40 minutes) nearly eliminates low-Mg²⁺-induced epileptiform recurrent short discharge frequency in combined entorhinal cortex-hippocampal slices, reducing activity to 1.60% of baseline^[1].
4-Methyloctanoic acid (1 mM) does not alter baseline transmission or short-term potentiation at mossy fibre to CA3 synapses in normal rat hippocampal slices^[1].
4-Methyloctanoic acid (1 mM) potently inhibits forskolin-induced mossy fibre response enhancement in normal rat hippocampal slices, reducing fEPSP amplitude to 231.67% of baseline^[1].
4-Methyloctanoic acid (0.1-1 μM; 40 min) potently reduces PTZ-induced epileptiform discharge frequency in rat entorhinal cortex-hippocampus slices, with greater efficacy than VPA at 0.5 μM and 1 μM concentrations^[2].
4-Methyloctanoic acid is potent in blocking chemotactic cell movement via inhibition of phosphoinositide production in Dictyostelium discoideum cells^[3].
4-Methyloctanoic acid (0.5 mM; 3 min pre-treatment, 6 min labelling incubation) potently inhibits phosphoinositide synthesis in developed Dictyostelium AX2 cells, reducing PIP production to 12% of control levels, while simultaneously increasing cellular inositol levels^[6].
4-Methyloctanoic acid (up to 10 mM) does not inhibit human HDAC activity at concentrations up to 10 mM, unlike VPA which potently inhibits HDAC activity at these levels^[2].
4-Methyloctanoic acid (0.01-10 mM; 24 h) has minimal toxicity to human Huh7 hepatoma cells, with an IC₅₀ of 7.3 mM, indicating a lower hepatotoxic potential than some other medium chain fatty acids tested^[2]. In Vivo:4-Methyloctanoic acid (400 mg/kg; i.p.; single administration) terminates status epilepticus in rats, reduces the frequency and amplitude of electroencephalogram spike waves, suppresses behavioral seizures, and provides neuroprotective effects on the hippocampal CA1 and CA3 regions^[1].
4-Methyloctanoic acid (400-600 mg/kg; i.p.; single administration) completely terminates electroencephalographic and behavioral seizures in all tested animals, but fails to prevent hippocampal hilar neuron loss after seizure onset. However, it induces sedation in healthy male Sprague-Dawley rats, with severe sedation observed at 600 mg/kg^[2].
Radiolabeled 4-Methyloctanoic acid ([¹⁸F]-19) (59-740 kBq; intravenous injection; single administration) exhibits low initial brain uptake of 0.15 % dose/g in fasted male Wistar rats, and its brain radioactivity retention is mainly attributed to polar metabolites that can cross the blood-brain barrier^[4].
4-Methyloctanoic acid (100 µM; incorporated into standard fly food; continuous feeding; from mating through larval development) partially reverses impaired motor function in ALS Drosophila models, fully rescues presynaptic neurotransmitter release, alters NMJ morphology, and partially corrects ALS-associated metabolic dysregulation^[5].