Effects of ketamine and theophylline on excitatory and inhibitory amino acids-induced currents in acutely dissociated hippocampal cells of the rat

• Published in: Japanese Journal of Pharmacology 1995, Vol.67 (suppl.1), p.156-156
• Main Authors: Abe, Hideo, Motomura, Shigeru, Kitayama, Masatou, Sakai, Tesgphirp, Matsuki, Akitomo
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)46588-8

The use of ketamine and theophylline in combination during anesthesia is not uncommon. Asthmatic patients are often receiving theophylline at the time of surgery. ketamine has been shown to prevent increase in pulmonary resistance induced by antigen in animal model of asthma. Ketamine-theophylline-induced decrease in seizure threshold was reported in 1982. However, the concept of the mechanism of action of these two drugs has recently become controversial. The present study was designed to examine the direct actions of ketamine and theophylline in acutely dissociated mammalian central neurons by patchclamp technique (whole-cell mode). Glycine (10^-4 M)induced currents were decreased by ketamine and theophylline in a concentration-dependent manner, its IC_50 values were approximately 7 x 10^-4 M and 5 x 10^-4 M, respectively. The inhibitory effect of ketamine was much more enhanced by the combined administration of theophylline together. But these two drugs, either alone or in combination, had little effect on GABA (10^-5 M)induced currents. NMDA-induced currents enhanced by glycine (10^-6 M) were decreased by ketamine in a concentration-dependent manner. In contrast, they were small but weakly increased without glycine. These results suggest that the convulsions induced by the combination of ketamine and theophylline may be related to their blocking effects on the glycine receptors, since both ketamine and theophylline directly decreased glycine-induced currents.