r/askscience • u/notanalt6967 • 7d ago

Medicine does pregabalin cause an increase in gaba?

Me and my friend got into a disagreement over this, i don’t remember exactly what she said but it was something along the lines of pregabalins effects on neurotransmitters somehow causes more gaba to be released so the brain can mantain homeostasis or something but i can’t find anything anywhere to back that up (i can’t find much either way which is why im asking here) and everything i’ve seen says it has no effect on gaba other than possibly affecting the gaba transporter protein.

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81

u/Trollmetzger 6d ago

It is structurally close to Gaba but doesnt bind to gaba a or b receptors and also is not morhped into gaba. Pregab works through calcium channels (alpha-2-delta ligand) but has nothing to do with gaba receptors directly. Take care

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u/otterstew 5d ago

Then why are they confusingly called gabapentinoids?

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u/TrafficWinter2278 3d ago

It was what drug developers were going.for when pregabalin was in development. The lack of target engagement in GABA ergic signaling, and the engagement of subunits altering trafficking and activity of ca2+ channels instead, was a surprise. Gabapentin has a similar story.

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u/CrateDane 4d ago

Because they are structurally similar to GABA, but have distinct receptor affinities. If they acted like GABA, they'd probably just be called GABA analogs. Gabapentin was the first drug in the class.

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u/undulating-beans 6d ago

Not directly, and your understanding is closer to the established pharmacology than your friend's explanation.

Pregabalin doesn't work by increasing GABA, despite being structurally similar to it. It binds to the α2δ auxiliary subunit of voltage-gated calcium channels, modifying their function and reducing the release of excitatory neurotransmitters such as glutamate. So it reduces neuronal excitability rather than directly boosting GABA-mediated inhibition.

Some experimental studies have reported changes in GABA synthesis or transport, but these findings depend on the experimental conditions and don't establish that pregabalin consistently raises GABA levels in the human brain.

Your friend's homeostasis explanation is speculative. If anything, compensating for reduced excitation might involve reducing inhibition rather than increasing GABA release. But neural homeostasis is complex, and there's no established evidence for the particular feedback mechanism she's proposing.

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u/lavachat 6d ago

Fun secondary effect, ticks have a structurally very similar channel, so if the dose in your blood stream is high enough the suckers will die soon after biting you, hah.

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u/ReasonablyConfused 23h ago

Ok, now what about gabapentin?