Masuoka Takayoshi, Mikami Azusa, Yasuda Masa, Shinomiya Kazuaki, Kamei Chiaki
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
Eur J Pharmacol. 2007 Dec 8;576(1-3):77-82. doi: 10.1016/j.ejphar.2007.08.020. Epub 2007 Aug 23.
The effects of histamine H(1) receptor antagonists (promethazine, diphenhydramine, chlorphenilamine and triprolidine) on hippocampal theta rhythm during eight-arm radial maze performance were investigated using rats. Promethazine showed a significant increase in the number of total errors and working memory errors at doses of 10 and 20 mg/kg, and a significant increase was also observed in reference memory errors at a dose of 20 mg/kg. Diphenhydramine and chlorphenilamine at a dose of 20 mg/kg and triprolidine at a dose of 35 mg/kg also caused significant increases in the number of total, reference memory and working memory errors. Promethazine, diphenhydramine and chlorphenilamine, having potent anti-muscarinic receptor properties, increased hippocampal theta power during radial maze performance at a dose of 20 mg/kg. On the other hand, triprolidine, which has weak anti-muscarinic receptor properties compared with other histamine H(1) receptor antagonists, decreased theta power at a dose of 35 mg/kg. These results suggest that anti-muscarinic receptor properties rather than anti-histamine H(1) receptor properties may affect hippocampal theta power during spatial memory deficit induced by promethazine, diphenhydramine and chlorphenilamine.
使用大鼠研究了组胺H(1)受体拮抗剂(异丙嗪、苯海拉明、氯苯那敏和曲普利啶)对八臂放射状迷宫实验中大鼠海马θ节律的影响。异丙嗪在10和20mg/kg剂量时,总错误数和工作记忆错误数显著增加,在20mg/kg剂量时,参考记忆错误数也显著增加。20mg/kg剂量的苯海拉明和氯苯那敏以及35mg/kg剂量的曲普利啶也导致总错误数、参考记忆错误数和工作记忆错误数显著增加。具有强效抗毒蕈碱受体特性的异丙嗪、苯海拉明和氯苯那敏在20mg/kg剂量时,在放射状迷宫实验中增加了海马θ功率。另一方面,与其他组胺H(1)受体拮抗剂相比,具有较弱抗毒蕈碱受体特性的曲普利啶在35mg/kg剂量时降低了θ功率。这些结果表明,在异丙嗪、苯海拉明和氯苯那敏诱导的空间记忆缺陷期间,抗毒蕈碱受体特性而非抗组胺H(1)受体特性可能影响海马θ功率。