''THE EFFECT OF GABA ANTAGONISM ON OPIOID POTENTIATION : APOSSIBLE MECHANISM OF TRAMADOL ANALGESIA

Abstract

Activation of GABA receptors which are located spinally (GABA-B) and supraspinally (GABA-A) at the level of peri­ aquiductal gray PAG, can directly increase analgesic requirements of morphine. This requirements will obviously decrease in case that flumazenil (GABA-antagonist) is given together with morphine. So based on this concept the anti-GABA effect will add more efficacy to the analgesic drug.

Tramadol HCL is an analgesic drug used since 20 years ago world wide it's daily therapeutic dose for average adult is 400-600 mg/day. It has a weak opioid agonist effect through ).1-receptor, also it inhibit reuptake of 5HT and noradernaline neurotansmitters in higher supra-spinal centers. Intra-operative use of Tramadol was accompanied with some degree of awareness, with incidence of convulsive fits in higher toxic doses. This attract the attention to screen this drug pharmacologically and clinically to discover its possible anti-GABA effect and understand its analgesic mechanism more clearly and add more comprehension to .its efficacy.

This study was conducted in 2-ways:

l. Pharmacological : in which two designs of experimental tests were postulated:

A. Test experiment for behavioral responses of rats in which 30 rats were divided into equal groups (each of 5) in cages and assessing alertness, mobility, feeding, interaction with each other and response to auditory stimuli.