PMID- 2846121
OWN - NLM
STAT- MEDLINE
DCOM- 19881221
LR  - 20190613
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 461
IP  - 2
DP  - 1988 Oct 4
TI  - Paradoxical convulsant action of a novel non-competitive N-methyl-D-aspartate 
      (NMDA) antagonist, tiletamine.
PG  - 343-8
AB  - Intracerebroventricular (i.c.v.) injection of tiletamine, 0.001 mumol, a presumed 
      non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, protected 
      mice from convulsions induced by NMDA and quinolinate, but not from those induced 
      by excitatory amino acids interacting preferentially with non-NMDA receptors. At 
      higher doses, however, tiletamine induced convulsions by itself. 
      Tiletamine-induced convulsions were antagonized by the broad spectrum excitatory 
      amino acid antagonist, gamma-D-glutamylamino-methylsulphonate (gamma-D-GAMS), and 
      were potentiated by the competitive NMDA antagonist, 
      2-amino-7-phosphonohepatanoate (AP7). Intrathecal (i.t.) injection of tiletamine, 
      0.01-1.0 mumol, dose-dependently suppressed spinal flexor reflexes. Tiletamine, 
      0.01 and 0.1 mumol, failed to affect spinal Hoffman- (H-) reflexes, whereas 
      tiletamine, 1.0 mumol, led to a 50% increase of the H-reflex amplitude. It is 
      concluded that the anticonvulsant and reflex suppressant action of tiletamine are 
      due to antagonism of NMDA receptor-mediated excitation. The convulsant effect of 
      tiletamine and its excitatory effect on spinal H-reflexes at higher doses, 
      however, appear to be mediated by non-NMDA receptors.
FAU - Klockgether, T
AU  - Klockgether T
AD  - Max Planck Institute for Experimental Medicine, Gottingen, F.R.G.
FAU - Turski, L
AU  - Turski L
FAU - Schwarz, M
AU  - Schwarz M
FAU - Sontag, K H
AU  - Sontag KH
FAU - Lehmann, J
AU  - Lehmann J
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Anticonvulsants)
RN  - 0 (Cyclohexanes)
RN  - 0 (Quinolinic Acids)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Receptors, Neurotransmitter)
RN  - 2YFC543249 (Tiletamine)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - F6F0HK1URN (Quinolinic Acid)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - Aspartic Acid/analogs & derivatives/pharmacology
MH  - Cyclohexanes/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - N-Methylaspartate
MH  - Quinolinic Acid
MH  - Quinolinic Acids/pharmacology
MH  - Receptors, N-Methyl-D-Aspartate
MH  - Receptors, Neurotransmitter/drug effects/*physiology
MH  - Reflex, Monosynaptic/drug effects
MH  - Seizures/*chemically induced
MH  - Tiletamine/*pharmacology
EDAT- 1988/10/04 00:00
MHDA- 1988/10/04 00:01
CRDT- 1988/10/04 00:00
PHST- 1988/10/04 00:00 [pubmed]
PHST- 1988/10/04 00:01 [medline]
PHST- 1988/10/04 00:00 [entrez]
AID - 0006-8993(88)90265-X [pii]
AID - 10.1016/0006-8993(88)90265-x [doi]
PST - ppublish
SO  - Brain Res. 1988 Oct 4;461(2):343-8. doi: 10.1016/0006-8993(88)90265-x.