PMID- 3034195
OWN - NLM
STAT- MEDLINE
DCOM- 19870619
LR  - 20190903
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 59
IP  - 5
DP  - 1987 Feb
TI  - Interaction of the pesticide chlordimeform with adrenergic receptors in mouse 
      brain: an in vitro study.
PG  - 323-7
AB  - Chlordimeform (N'(4-chloro-o-tolyl)-N, N-dimethylformamidine; CDM) is a 
      formamidine insecticide acaricide whose major active metabolite is its 
      N-monomethyl analog, desmethylchlordimeform, (DCDM). While their pesticidal 
      action in invertebrates appears to be related to activation of octopamine 
      receptors, their mechanism of action in mammals has not been established. Because 
      of similarities between octopamine and adrenergic receptors and suggestions of 
      CDM and DCDM action on adrenoceptors, the in vitro interactions of CDM and DCDM 
      with adrenoceptors were studied. In mouse brain membrane preparations CDM 
      inhibited the binding of [3H]-clonidine to alpha 2- adrenoceptors and of 
      [3H]-WB4101 to alpha 1-adrenoceptors with IC50 values of 18.2 and 87 microM, 
      respectively. DCDM was a much more potent inhibitor, with IC50 values toward 
      alpha 2-, and alpha 1-adrenoceptors of 44 nM and 1 microM, respectively. Both 
      compounds were only weak inhibitors of the binding of [3H]-dihydroalprenolol to 
      beta-adrenoceptors and of [3H]-quinuclidinyl benzilate to muscarinic receptors 
      and were inactive toward benzodiazepines and gamma aminobutyric acid (GABAA) 
      receptors. Inhibition of [3H]-clonidine binding by both compounds was 
      competitive, as indicated by a decreased receptor affinity without changes in 
      receptor density. Interaction of CDM and DCDM with [3H]-WB4101 binding, on the 
      other hand, was more complex, and not of the competitive type. These results show 
      that CDM and its metabolite DCDM can interact directly in vitro with 
      alpha-adrenergic receptors, suggesting that these receptors could mediate some of 
      the effects of CDM and DCDM in vivo.
FAU - Costa, L G
AU  - Costa LG
FAU - Murphy, S D
AU  - Murphy SD
LA  - eng
GR  - ES-03424/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Amidines)
RN  - 0 (Dioxanes)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Adrenergic)
RN  - 0 (Receptors, GABA-A)
RN  - 21787-80-4 (demethylchlordimeform)
RN  - 2763-96-4 (Muscimol)
RN  - 60106-89-0 (Dihydroalprenolol)
RN  - 6581-06-2 (Quinuclidinyl Benzilate)
RN  - E9H51OIT2B ((2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane)
RN  - GXA8FP6Y9C (Chlorphenamidine)
RN  - MN3L5RMN02 (Clonidine)
RN  - Q3JTX2Q7TU (Diazepam)
SB  - IM
MH  - Amidines/*toxicity
MH  - Animals
MH  - Brain Chemistry/*drug effects
MH  - Chlorphenamidine/analogs & derivatives/*toxicity
MH  - Clonidine/pharmacology
MH  - Diazepam/pharmacology
MH  - Dihydroalprenolol
MH  - Dioxanes/metabolism
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Male
MH  - Mice
MH  - Muscimol/metabolism
MH  - Proteins/metabolism
MH  - Quinuclidinyl Benzilate/toxicity
MH  - Receptors, Adrenergic/*drug effects
MH  - Receptors, GABA-A/metabolism
EDAT- 1987/02/01 00:00
MHDA- 1987/02/01 00:01
CRDT- 1987/02/01 00:00
PHST- 1987/02/01 00:00 [pubmed]
PHST- 1987/02/01 00:01 [medline]
PHST- 1987/02/01 00:00 [entrez]
AID - 10.1007/BF00295083 [doi]
PST - ppublish
SO  - Arch Toxicol. 1987 Feb;59(5):323-7. doi: 10.1007/BF00295083.