IS THE MODULATION EFFECT OF MIDAZOLAM ON MORPHINE INDUCED ANTINOCICEPTION TIME DEPENDENT?

Year 2019, , 1573 - 1582, 15.08.2019

Seyfullah Oktay Arslan , İşıl Özkoçak Turan

https://doi.org/10.30569/adiyamansaglik.559772

Abstract

Aim: The aim
of this study was to investigate the effects of midazolam, morphine and
midazolam-morphine on nociception. Benzodiazepines are known to influence
opioid analgesia, and variations can be expected in the interaction between
benzodiazepines and opioids at different times of the day.

Method: The
effects of midazolam, morphine, and midazolam-morphine combination on
nociception were evaluated with tail flick test in mice, with together the
time-dependent changes. Midazolam has not any antinociceptive effect and it
inhibited in a fashion dose-dependent the antinociceptive effect of morphine.

Results: Control
group injected with saline displayed a significant diurnal rhythmicity in the
tail flick test significantly. Saline control group’s response latency at light
hour (at 16.00 h, P < 0.05) was
shorter than that at late dark hour (at 04.00 h) and early morning hour (at
08.00 h). Morphine injected animals had shorter response latencies in light
hours (at 12.00 and 16.00 h, P <
0.01) than at late dark hour (at 04.00 h) and early morning hour (at 08.00 h).
When midazolam was used in combination with morphine, the tail flick response
latencies became significant shorter clearly at every experiment times (P < 0.001), however this inhibition
was slightly lower at 04.00 h than the other hours.

Conclusion: Our
results indicate that midazolam antagonism on morphine antinociception have not
diurnal rhythmicity, however it may only slight decreased at late dark hours of
day.

Keywords

Morphine, midazolam, antagonism, antinociception, circadian rhythm, tail flick, mice

MIDAZOLAM'IN MORFİNE İLİŞKİN MODÜLASYON ETKİSİ ANTİNOKİKASYON ZAMANI BAĞIMLI MI?

Abstract

Amaç: Bu
çalışmanın amacı, midazolam, morfin ve midazolam-morfin kombinasyonunun
nosisepsiyon üzerindeki etkilerini araştırmaktır. Benzodiazepinlerin opioid
analjezisini etkilediği bilinmektedir ve günün farklı zamanlarında
benzodiazepinler ve opioidler arasındaki etkileşimlerde değişiklikler
beklenebilir. Yöntem: Midazolam, morfin
ve midazolam-morfin kombinasyonunun nosisepsiyon üzerindeki etkileri farelerde
kuyruk flick testi ile birlikte zamana bağlı değişiklikler ile değerlendirildi.
Midazolam'ın antinosiseptif bir etkisi yoktur ve morfinin antinosiseptif
etkisini doza bağlı bir şekilde inhibe eder.

Bulgular: Salin
enjekte edilen kontrol grubu, kuyruk flick testinde anlamlı bir günlük
ritmikliği gösterdi. Tuzlu kontrol grubunun ışık saatindeki (16.00 saatte, P
<0.05) saat gecikme süresi karanlık saatlerde (04.00 saatte) ve sabah
saatlerinde (08.00'de) daha kısa idi. Enjekte edilen morfinler, aydınlık
saatlerde (12.00 ve 16.00 saat, P <0.01) karanlık saatlerin geç saatlerinde
(04.00 saatte) ve sabah saatlerinin (saat 08.00'de) daha kısa tepki gecikme
sürelerine sahipti. Midazolam morfin ile birlikte kullanıldığında, kuyruk
hareket yanıtı gecikme süreleri, her deney zamanında (P <0.001) açıkça
belirgin şekilde kısaldı, ancak bu inhibisyon, diğer saatlere göre 04.00 saatte
biraz daha düşüktü. Sonuç: Morfin
antinosisepsiyonundaki midazolam antagonizmasının günlük ritmik olmadığına
işaret etse de, günün karanlık saatlerinde sadece hafif bir şekilde azalabilir.

Keywords

Morphine, midazolam, antagonism, antinociception, circadian rhythm, tail flick, mice

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