Rao S G, Hrishikeshavan H J, Guruswami M N
Department of Pharmacology, Kasturba Medical College, Manipal, India.
Funct Neurol. 1990 Oct-Dec;5(4):353-60.
Three pharmacological tools namely zimelidine, danitracen and MK 212, were selected to examine the nature of involvement of serotonergic neurotransmission in catalepsy, an undesirable side effect following administration of neuroleptics in rats. Reserpine and haloperidol were chosen as cataleptogenic challenges. Zimelidine, a serotonin (5-HT) reuptake blocker, inhibited the manifestation of reserpine and haloperidol induced catalepsy. However, a dose dependent effect could not be demonstrated beyond 30 mumoles/kg. Danitracen, a 5-HT receptor blocker, prevented the occurrence of the symptoms that were observed following reserpine treatment but it could not elicit blockade of haloperidol response. MK 212, an S2 (5-HT2) receptor stimulant forestalled the occurrence of reserpine syndrome at lower doses but exhibited cataleptogenic effects at higher doses. Besides, MK 212 failed to influence catalepsy following administration of haloperidol. It appears that 5-HT exerts a homoeostatic control in the regulatory neuraxis in neuroleptic induced neurological side effects.
选用了三种药理学工具,即齐美利定、丹曲林和MK 212,来研究5-羟色胺能神经传递在僵住症中的作用性质,僵住症是大鼠服用抗精神病药物后出现的一种不良副作用。选择利血平和氟哌啶醇作为致僵住症刺激物。齐美利定是一种5-羟色胺(5-HT)再摄取阻滞剂,可抑制利血平和氟哌啶醇所致僵住症的表现。然而,超过30微摩尔/千克时未显示出剂量依赖性效应。丹曲林是一种5-HT受体阻滞剂,可预防利血平治疗后出现的症状,但不能阻断氟哌啶醇反应。MK 212是一种S2(5-HT2)受体兴奋剂,在较低剂量时可预防利血平综合征的发生,但在较高剂量时表现出致僵住症作用。此外,MK 212对氟哌啶醇给药后的僵住症没有影响。看来5-HT在抗精神病药物所致神经副作用的调节神经轴中发挥着稳态控制作用。