Some pharmacological and histological studies on the effect of neostigmine injected intrathecally

ABSTRACT

The spinal delivery of the cholinesterase inhibitor neostigmine yields analgesia and augments the analgesic effect of alpha-2 [alpha-2] agonist. To assess its activity, histological and pharmacological studies were designed to define its effect in two species; rats and cats. Pharmacological assessment of intrathecally injected [it] neostigmine in cats showed a gradual increase in mean blood pressure [MBP] and heart rate [HR] at doses 2 - 16 micro g /kg while a decrease in MBP and HR occurred at doses 32 - 64 micro g /kg. The intrathecal injection of atropine and phentolamine abolished the increase in MBP and HR produced by [it] neostigmine [4 micro g /kg]. In spinal cat preparation [it] neostigmine produced rapid rise in MBP at small [4 micro g /kg] and large doses [64 micro g /kg]. In this study neostigmine counteracts the hypotensive effect and bradycardia produced by intrathecal injection of alpha-2 agonist clonidine. Histological study was performed on rats. They were divided into 5 groups representing control and 4 groups treated by neostigmine at 25, 50, 75 and 100 micro g/kg. After each injection, the animals were assessed for general behavior, and function. Arousal, motor coordination and motor tone measurement [A, MC and MT] revealed that Intrathecal injection of neostigmine resulted in dose-dependent decreased arousal, and motor coordination, and dose-dependent increase in motor tone. The quantitative histological and cytochemical data demonstrated an initial increase in the nucleo-cytoplasmic ratio of the anterior horn cells up to 75 ug/kg followed by a decline in 100 ug/kg- treated animals. The cytoplasmic RNA content of the anterior horn cells showed an increase in the optical density that reached a maximum at 50 ug/kg followed by a decline at higher doses. The Golgi bodies increased in the cytoplasm of 25 ug/kg treated animals, the level became constant up til 75 ug/kg, and started to decline at 100 ug/kg. There was no change in the quantity of the myelinated nerve fibers, however, there was a dose dependent decline in their stainability with silver. These results provide an evidence that the adverse events from neostigmine injected intrathecally appear to be affected by the dose injected which could be important in clinical practice