1991 Fiscal Year Final Research Report Summary
Interaction of various-non-steroidal anti-inflammatories and quinolone antimicrobials on GABA response in rat dissociated hippocampal pyramidal neurons
| Project/Area Number |
02807213
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
NAKAYE Toshio Tohoku Univ. Sch. Med. Assistant Professor, 医学部, 助手 (20155659)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TOKUTOMI Naofumi Tohoku Univ. Sch. Med. Assistant Professor, 医学部, 助手 (30227582)
AKAIKE Norio Tohoku Univ. Sch. Med. Professor, 医学部, 教授 (30040182)
|
|---|
| Project Period (FY) |
1990 – 1991
|
| Keywords | Rat hippocampal neuron / gamma-Aminobutyric acid-A response / Non-steroidal anti-inflammatory / Quinolone |
|---|
| Research Abstract |
1. Interactions of quinolone antibiotics and non-steroidal anti-inflammatory drugs(NSAIDs)with the y-aminobutyric acid-A(GABA_A)receptor-chloride channel complex in pyramidal neurons freshly dissociated from the hippocampal CAl region of rats were investigated in whole cell mode, using the patch-clamp technique under voltage-clamp conditions.
2. Quinolones in clinical doses had no effects on 5the GABA-gated Cl^- current(I_<C1>)but slightly suppressed the response at concentrations over 10^<-5> M. A metabolite of fenbufen, 4-biphenylacetic acid(BPA, one of NSAIDs)itself, also had little effect on the GABA response at therapeutic concentrations.
3. Coadministraiton of one of quinolones and BPA markedly suppressed the GABA-gated I with increase in each of them in a concentration-dependent manner. There was a parallel shift of the concentration-response curve for GABA to the right but with no effect on the maximum response, indicating a competitive antagonism. The inhibitory potency of antibiotics in combination with BPA was in the order of norfloxacin>>enoxacm>cyprofloxacin>pipemidic acid>>ofloxacin>cinoxacin = piromidic acid = nalidixic acid = 0.
4. In the presence of norfloxacin(NFLX), one of quinolones, some NSAIDs suppressed the GABA response in a concentration-dependent manner. The inhibitory potency of NSAISs was BPA>>indomethacin = naproxen>mefenamic acid>diclofenac>piroxicarn.
5. It was concluded that, in the presence of an anti-inflammatory agent(BPA), the quinolone antibiotics decrease the affinity of GABA_A receptors. And, in the presence of a quinolone(NFLX), BPA, indomethacin and naproxen may induce the epileptogenic neurotoxicities via pharmacological interaction with GABA_A receptor.
|
