Adenosine A1 antagonist (CBZ effect)
Adenosine A1 receptor antagonist (carbamazepine effect)
- Not wake-promoting: caffeine’s arousal is an A2A effect, not A1
- Carbamazepine blocks adenosine A1 receptors — the same receptor action as caffeine
- Acutely that is pro-epileptic: A1 blockade enhances excitatory transmission onto hippocampal CA1 pyramidal cells at therapeutic concentrations, with no matching change in inhibition
- Chronic exposure upregulates A1 receptors, a compensatory swing
- In astrocyte culture the upregulation appears only where basal A1 is low, and brings a coupling to phospholipase C that was not there before (1999)
- The evidence is not uniform: oral carbamazepine had no major effect on mouse brain A1 receptors (1991), and chronic carbamazepine down-regulates A2 receptors
- The resulting rise in A1 signaling is a proposed, not established, antimanic mechanism
- The receptor papers themselves make no antimanic claim
Drugs with this mechanism (4)
- Carbamazepine — Anticonvulsant/mood stabilizer and potent autoinducer; HLA-B*1502 rash risk.
- Carbamazepine ER capsules — Bead-filled extended-release carbamazepine capsule; can be opened and sprinkled.
- Carbamazepine ER (Equetro) — Carbamazepine ER capsule - the only carbamazepine approved for acute bipolar mania.
- Carbamazepine XR — Extended-release carbamazepine for seizures and trigeminal neuralgia; potent enzyme inducer.
Self-check
- What is the acute electrophysiologic direction of carbamazepine's A1 blockade?
Pro-epileptic: increased excitatory transmission. - Is increased A1 signaling an established antimanic mechanism of carbamazepine?
No; it is proposed.
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