Trzeciakowski J P, Frye G D
Eur J Pharmacol. 1986 May 27;124(3):231-41. doi: 10.1016/0014-2999(86)90224-4.
In awake rats, ranitidine was more effective than cimetidine in elevating blood pressure following intracerebroventricular (i.c.v.) injection, yet neither drug affected the hypotensive response to subsequent injections of muscimol (8.8 nmol i.c.v.). Bicuculline (0.01 nmol) microinjected into the inferior colliculus of rats caused clonic seizures whereas cimetidine (100 nmol) had no effect. The antihistamines did not prevent GABAB receptor-mediated inhibition of twitch responses in transmurally stimulated guinea-pig ileum. Ranitidine potentiated rather than inhibited GABAA receptor-mediated contractions of ileum longitudinal muscle. Cimetidine had no effect on these responses except at high concentrations (3 X 10(-4) M) which caused a slight dextral shift in the contractile response curve for GABA that may be attributed to antimuscarinic actions of cimetidine. Taken together, these data do not support the concept that the centrally mediated pressor effects of H2 antagonists are caused by GABA receptor blockade.
在清醒大鼠中，脑室内（i.c.v.）注射后，雷尼替丁在升高血压方面比西咪替丁更有效，但两种药物均未影响随后注射蝇蕈醇（8.8 nmol i.c.v.）引起的降压反应。向大鼠下丘脑中微量注射荷包牡丹碱（0.01 nmol）会引起阵挛性惊厥，而西咪替丁（100 nmol）则无作用。这些抗组胺药不能阻止GABAB受体介导的对经壁刺激的豚鼠回肠抽搐反应的抑制。雷尼替丁增强而非抑制GABAA受体介导的回肠纵肌收缩。西咪替丁对这些反应无影响，除非在高浓度（3×10⁻⁴ M）时，此时会使GABA的收缩反应曲线略有右旋移位，这可能归因于西咪替丁的抗毒蕈碱作用。综上所述，这些数据不支持H2拮抗剂的中枢介导升压作用是由GABA受体阻断引起的这一概念。
