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Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats.
Acta Anaesthesiol Scand. 1999 Aug; 43(7):753-9.AA

Abstract

BACKGROUND

Intravenous administration of N-methyl-D-aspartate (NMDA) receptor antagonists and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists reportedly reduce the minimum alveolar anaesthetic concentration (MAC) for inhalation anaesthetics. If pain perception can be prevented by the intrathecal administration of antinociceptive receptor antagonists, these agents may reduce the requirements for inhalation anaesthetics. We studied the effect of intrathecal administration of an AMPA/kainate receptor antagonist, a metabotropic glutamate (mGlu) receptor antagonist and co-administration of NMDA and a neurokinin-1(NK-1) receptor antagonist drugs at low doses on the MAC.

METHODS

After Wistar rats (n=36) were fitted with indwelling intrathecal catheters, the MAC of isoflurane was determined following intrathecal administration of a non-NMDA receptor antagonist (CNQX) at 10 microg, a mGlu receptor antagonist (AP3) at 10 microg, or a combination of NMDA receptor antagonist (APV) at 0.01 microg to 1 microg with NK-1 receptor antagonist (CP96345, CP) at 0.1 microg to 10 microg. Subsequently, a reversal dose of intrathecal NMDA with substance P (SP) was administered, and the MAC of isoflurane was redetermined. Conscious rats (n=15) were also examined for the presence of locomotor dysfunction following the intrathecal co-administration of APV and CP.

RESULTS

Neither CNQX nor AP3 reduced the MAC of isoflurane. APV at 0.01 microg plus CP at 1 microg, as well as APV at 0.1 microg plus CP at 10 microg, reduced the MAC of isoflurane, with respective reductions of 7.6% and 14%; (P<0.05). Co-administration of NMDA plus SP reversed the decrease in the MAC of isoflurane. Locomotive activity was not changed.

CONCLUSIONS

The NMDA receptor and the NK-1 receptor are important determinants of the MAC of isoflurane, exerting this influence by inhibition of pain transmission in the spinal cord, while mGlu and AMPA receptors have no effect on the MAC of isoflurane.

Authors+Show Affiliations

Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Maebashi, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10456816

Citation

Ishizaki, K, et al. "Intrathecal Co-administration of NMDA Antagonist and NK-1 Antagonist Reduces MAC of Isoflurane in Rats." Acta Anaesthesiologica Scandinavica, vol. 43, no. 7, 1999, pp. 753-9.
Ishizaki K, Sasaki M, Karasawa S, et al. Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats. Acta Anaesthesiol Scand. 1999;43(7):753-9.
Ishizaki, K., Sasaki, M., Karasawa, S., Obata, H., Nara, T., & Goto, F. (1999). Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats. Acta Anaesthesiologica Scandinavica, 43(7), 753-9.
Ishizaki K, et al. Intrathecal Co-administration of NMDA Antagonist and NK-1 Antagonist Reduces MAC of Isoflurane in Rats. Acta Anaesthesiol Scand. 1999;43(7):753-9. PubMed PMID: 10456816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats. AU - Ishizaki,K, AU - Sasaki,M, AU - Karasawa,S, AU - Obata,H, AU - Nara,T, AU - Goto,F, PY - 1999/8/24/pubmed PY - 1999/8/24/medline PY - 1999/8/24/entrez SP - 753 EP - 9 JF - Acta anaesthesiologica Scandinavica JO - Acta Anaesthesiol Scand VL - 43 IS - 7 N2 - BACKGROUND: Intravenous administration of N-methyl-D-aspartate (NMDA) receptor antagonists and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists reportedly reduce the minimum alveolar anaesthetic concentration (MAC) for inhalation anaesthetics. If pain perception can be prevented by the intrathecal administration of antinociceptive receptor antagonists, these agents may reduce the requirements for inhalation anaesthetics. We studied the effect of intrathecal administration of an AMPA/kainate receptor antagonist, a metabotropic glutamate (mGlu) receptor antagonist and co-administration of NMDA and a neurokinin-1(NK-1) receptor antagonist drugs at low doses on the MAC. METHODS: After Wistar rats (n=36) were fitted with indwelling intrathecal catheters, the MAC of isoflurane was determined following intrathecal administration of a non-NMDA receptor antagonist (CNQX) at 10 microg, a mGlu receptor antagonist (AP3) at 10 microg, or a combination of NMDA receptor antagonist (APV) at 0.01 microg to 1 microg with NK-1 receptor antagonist (CP96345, CP) at 0.1 microg to 10 microg. Subsequently, a reversal dose of intrathecal NMDA with substance P (SP) was administered, and the MAC of isoflurane was redetermined. Conscious rats (n=15) were also examined for the presence of locomotor dysfunction following the intrathecal co-administration of APV and CP. RESULTS: Neither CNQX nor AP3 reduced the MAC of isoflurane. APV at 0.01 microg plus CP at 1 microg, as well as APV at 0.1 microg plus CP at 10 microg, reduced the MAC of isoflurane, with respective reductions of 7.6% and 14%; (P<0.05). Co-administration of NMDA plus SP reversed the decrease in the MAC of isoflurane. Locomotive activity was not changed. CONCLUSIONS: The NMDA receptor and the NK-1 receptor are important determinants of the MAC of isoflurane, exerting this influence by inhibition of pain transmission in the spinal cord, while mGlu and AMPA receptors have no effect on the MAC of isoflurane. SN - 0001-5172 UR - https://www.unboundmedicine.com/medline/citation/10456816/Intrathecal_co_administration_of_NMDA_antagonist_and_NK_1_antagonist_reduces_MAC_of_isoflurane_in_rats_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0001-5172&amp;date=1999&amp;volume=43&amp;issue=7&amp;spage=753 DB - PRIME DP - Unbound Medicine ER -