PMID- 7797443
OWN - NLM
STAT- MEDLINE
DCOM- 19950801
LR  - 20190723
IS  - 0021-8820 (Print)
IS  - 0021-8820 (Linking)
VI  - 48
IP  - 5
DP  - 1995 May
TI  - Structural features resulting in convulsive activity of carbapenem compounds: 
      effect of C-2 side chain.
PG  - 408-16
AB  - The neurotoxicity of meropenem was much lower than that of both imipenem and 
      panipenem after intraventricular administration to mice. To clarify the major 
      structural features responsible for the induction of convulsions by carbapenem 
      antibiotics, the structure-activity relationship on convulsant activity was 
      investigated in N-acetyl-2-pyrroline and cyclopentene derivatives which 
      correspond to the 5-membered ring containing the C-2 side chain of carbapenem 
      antibiotics. Among these derivatives, compounds with strong basicity in the side 
      chain showed convulsant activity similar to that of the parent carbapenem 
      compounds. In addition to the strength of the basicity of the amino group, the 
      distance from the carboxyl to the amino group and steric crowding around the 
      amino group also appeared to play an important role in the induction of 
      convulsions. The results of gamma aminobutyric acid (GABAA) receptor binding 
      assays indicated that the induction of convulsions was caused predominantly by 
      the inhibition of GABAA-mediated inhibitory transmission. However, the in vivo 
      convulsant activity of some of these compounds did not correlate with their in 
      vitro inhibitory effect on GABAA receptor binding.
FAU - Sunagawa, M
AU  - Sunagawa M
AD  - Development Research Laboratory I, Sumitomo Pharmaceuticals Research Center, 
      Osaka, Japan.
FAU - Matsumura, H
AU  - Matsumura H
FAU - Sumita, Y
AU  - Sumita Y
FAU - Nouda, H
AU  - Nouda H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - J Antibiot (Tokyo)
JT  - The Journal of antibiotics
JID - 0151115
RN  - 0 (Receptors, GABA)
RN  - 0 (Thienamycins)
RN  - 71OTZ9ZE0A (Imipenem)
RN  - FV9J3JU8B1 (Meropenem)
RN  - W9769W09JF (panipenem)
SB  - IM
MH  - Animals
MH  - Imipenem/chemistry/*toxicity
MH  - Meropenem
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Receptors, GABA/drug effects/metabolism
MH  - Seizures/*chemically induced
MH  - Structure-Activity Relationship
MH  - Thienamycins/chemistry/*toxicity
EDAT- 1995/05/01 00:00
MHDA- 1995/05/01 00:01
CRDT- 1995/05/01 00:00
PHST- 1995/05/01 00:00 [pubmed]
PHST- 1995/05/01 00:01 [medline]
PHST- 1995/05/01 00:00 [entrez]
AID - 10.7164/antibiotics.48.408 [doi]
PST - ppublish
SO  - J Antibiot (Tokyo). 1995 May;48(5):408-16. doi: 10.7164/antibiotics.48.408.