Abstract | INTRODUCTION: METHODS: Following pre-treatment with verapamil (20 mg/kg) or a saline solution male Sprague Dawley rats were injected with imipramine (15 mg/kg). Two hours later, the animals were sacrificed, trunk blood collected and brain regions dissected out. High performance liquid chromatography (HPLC) was used to quantitate antidepressant drug concentrations in all samples. RESULTS:
Verapamil pre-treatment significantly elevated imipramine concentrations in all brain regions studied. The effect was most pronounced in the brainstem and frontal cortex where we observed in excess of a doubling in the brain region: serum ratios. CONCLUSION: Our results verify inhibition of Pgp as a potential mechanism of action for verapamil during treatment resistant depression. The implications of these findings are discussed in the context of novel treatment strategies in depression.
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Authors | Gerard Clarke, Siobhain M O'Mahony, John F Cryan, Timothy G Dinan |
Journal | Human psychopharmacology
(Hum Psychopharmacol)
Vol. 24
Issue 3
Pg. 217-23
(Apr 2009)
ISSN: 1099-1077 [Electronic] England |
PMID | 19212940
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antidepressive Agents, Tricyclic
- Calcium Channel Blockers
- Verapamil
- Imipramine
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(antagonists & inhibitors)
- Animals
- Antidepressive Agents, Tricyclic
(blood, pharmacokinetics)
- Brain
(anatomy & histology, drug effects, metabolism)
- Calcium Channel Blockers
(pharmacology)
- Chromatography, High Pressure Liquid
(methods)
- Imipramine
(blood, pharmacokinetics)
- Male
- Rats
- Rats, Sprague-Dawley
- Tissue Distribution
(drug effects)
- Verapamil
(pharmacology)
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