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The effect of theophylline on essential tremor: the possible role of GABA
Abstract:
The chronic administration of theophylline was studied in twenty patients with essential tremor in a double-blind cross-over trial. The tremor was improved significantly after four weeks of treatment. In mice the chronic administration of theophylline was compared with propranolol on the modulation by adenosine, 5-HT, (-)isoprenaline or GABA of NMDA-induced depolarisation of neocortical slices. Adenosine depolarisation was abolished by two-weeks treatment with theophylline but not propranolol. Potentiation by (-)isoprenaline of NMDA responses was reduced by theophylline (100 mg/kg/day) and propranolol treatment (25 mg/kg/day), but a lower dose of propranolol further increased it. The enhancement by 5-HT of NMDA-induced depolarisation was unaffected by the pretreatment with theophylline, while the higher dose of propranolol blocked it. GABA caused no significant change of NMDA depolarisation in control slices, but after theophylline treatment (100 mg/kg/day) and propranolol administration at both doses it significantly potentiated NMDA depolarisation. The enhancement of GABA sensitivity might be an important common factor in decreasing the essential tremor after propranolol and theophylline treatment.
Insights
Theophylline significantly improved essential tremor in patients. In mice, theophylline and propranolol altered brain responses, with both drugs enhancing GABA sensitivity, a potential mechanism for tremor reduction.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Neurology
Background:
- Essential tremor is a common neurological disorder.
- Theophylline and propranolol are used to manage essential tremor.
- The underlying mechanisms of action for these drugs are not fully understood.
Purpose of the Study:
- To investigate the efficacy of theophylline in treating essential tremor.
- To compare the effects of theophylline and propranolol on neurotransmitter modulation in mouse neocortical slices.
- To explore potential common mechanisms of action for both drugs in tremor reduction.
Main Methods:
- Double-blind, cross-over trial in twenty patients with essential tremor.
- In vitro study using mouse neocortical slices to assess NMDA-induced depolarization.
- Chronic administration of theophylline and propranolol in mice, followed by testing modulation by adenosine, 5-HT, (-)isoprenaline, and GABA.
Main Results:
- Theophylline significantly improved essential tremor in patients after four weeks.
- Theophylline abolished adenosine-mediated depolarization in mouse brain slices.
- Both theophylline and propranolol enhanced GABA-mediated potentiation of NMDA responses, suggesting increased GABA sensitivity.
Conclusions:
- Theophylline is effective in reducing essential tremor.
- Theophylline and propranolol may exert their anti-tremor effects through a common mechanism involving enhanced GABAergic neurotransmission.
- Further research is warranted to elucidate the precise molecular pathways involved.