Characterization of the anticonvulsant activity of doxepin in various experimental seizure models in mice.
Journal Title: Pharmacological Reports - Year 2009, Vol 61, Issue 2
Abstract
In this paper, the anticonvulsant characteristics of doxepin were evaluated in numerous experimental seizure models, including maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, isoniazid (ISO)-, 3-mercaptopropionic acid (3-MP)-, bicuculline (BIC)-, thiosemicarbazide (THIO)-, and strychnine (STR)-induced seizures. In addition, the acute adverse-effect profile of doxepin with respect to impairment of motor coordination was assessed with a mouse rotarod test. The evaluation of the time-course and dose-response relationships for doxepin provided evidence that the peak maximum anticonvulsant activity and acute adverse effects occurred 5 min after intraperitoneal (ip) administration. The results also revealed that doxepin had excellent anticonvulsant activity against maximal electroshock-induced seizures in mice with a median effect value (ED(50)) of 6.6 mg/kg. The assessment of acute adverse effects in the rotarod test revealed that doxepin induced acute neurotoxicity, and its median toxic dose (TD(50)) was 26.4 mg/kg. Additionally, doxepin showed anticonvulsant activity in several chemically-induced seizure models, including ISO, 3-MP, BIC, and THI. Based on this study, we can conclude that the antidepressant drug doxepin may be useful for treatment of depression in patients with epilepsy due to its short time to peak maximum anticonvulsant activity after ip administration (5 min) and remarkable anticonvulsant activity (6.6 mg/kg).
Authors and Affiliations
Xian-Yu Sun, Lei Zhang, Cheng-Xi Wei, Hu-Ri Piao, Zhe-Shan Quan
Keywords
Related Articles
- EP ID EP118684
- DOI -
- Views 97
- Downloads 0
Endogenous steroids are responsible for lactoferrin-induced myelopoiesis in mice.
Our previous study revealed that lactoferrin (LF) significantly increases mobilization of the myelocytic lineage in mice. The aim of our current investigation was to determine whether activation of the hypothalamic-pitui...
Stiripentol. A novel antiepileptic drug.
Epilepsy is one of the most widespread pathologies of human brain, affecting approximately 1% of world population. Despite the development of new methods of seizure control, chronic administration of antiepileptic drugs...
Activation of the NMDA/glutamate receptor complex antagonizes the NMDA antagonist-induced antidepressant-like effects in the forced swim test.
The antidepressant activity of NMDA receptor antagonists has been demonstrated, and their mechanism of action was based on the assumption of their selectivity for the NMDA receptor only. However, no direct evidence for t...
Effects of etoricoxib on the pharmacokinetics of phenytoin.
Etoricoxib is presently the most commonly prescribed cyclooxygenase-2 (Cox-2) inhibitor for chronic pain and inflammatory conditions. In clinical practice, phenytoin and etoricoxib are used in chronic conditions of gener...
Platelet interaction with progenitor cells: vascular regeneration or inquiry?
Increasing evidence supports the role of stem and progenitor cells in vascular regeneration or injury. Following tissue ischemia, progenitor cells are mobilized from their bone marrow or peripheral niches into circulatio...