Structure-activity Studies on the Potentiation of Benzodiazepine Receptor Binding by Ethylenediamine Analogues and Derivatives

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1983 Aug 1

PMID 6317124

Citations 2

Authors

P F Morgan

T W Stone

Affiliations

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Abstract

The effect of ethylenediamine analogues on in vitro binding of [3H]-diazepam to crude cerebral cortical synaptosomal membranes in the rat was studied. Ethylenediamine significantly increased [3H]-diazepam binding to a maximum potentiation of 154% control (EC50 = 1.8 X 10(-4) M) and was the most active compound studied in terms of both potency and the maximum potentiation observed. Potentiation of [3H]-diazepam binding by ethylenediamine analogues is dependent on carbon-chain length, appears to require two terminal amino groups, and is not observed in the rigid analogues studied. Potentiation of [3H]-diazepam binding by ethylenediamine analogues is mediated largely by a change in receptor number and not receptor affinity. Results are discussed in terms of the possible nature of the ethylenediamine binding site.

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References

Takeuchi A, Takeuchi N . A study of the action of picrotoxin on the inhibitory neuromuscular junction of the crayfish. J Physiol. 1969; 205(2):377-91. PMC: 1348609. DOI: 10.1113/jphysiol.1969.sp008972. View

Feltz A . Competitive interaction of beta-guanidino propionic acid and gamma-aminobutyric acid on the muscle fibre of the crayfish. J Physiol. 1971; 216(2):391-401. PMC: 1331945. DOI: 10.1113/jphysiol.1971.sp009531. View

Anderson E, Haas H, Hosli L . Comparison of effects of noradrenaline and histamine with cyclic AMP on brain stem neurones. Brain Res. 1973; 49(2):471-5. DOI: 10.1016/0006-8993(73)90445-9. View

Brookes N . Werman R:The cooperativity of -aminobutyric action on the membrane of locust muscle fibers. Mol Pharmacol. 1973; 9(4):571-9. View

Polc P, Mohler H, Haefely W . The effect of diazepam on spinal cord activities: possible sites and mechanisms of action. Naunyn Schmiedebergs Arch Pharmacol. 1974; 284(4):319-37. DOI: 10.1007/BF00504702. View

Constanti A, Nistri A . A comparative study of the action of gamma-aminobutyric acid and piperazine on the lobster muscle fibre and the frog spinal cord. Br J Pharmacol. 1976; 57(3):347-58. PMC: 1667242. DOI: 10.1111/j.1476-5381.1976.tb07673.x. View

Curtis D, Lodge D, Johnston G, Brand S . Central actions of benzodiazepines. Brain Res. 1976; 118(2):344-7. DOI: 10.1016/0006-8993(76)90723-x. View

Phillis J . The role of cyclic nucleotides in the CNS. Can J Neurol Sci. 1977; 4(3):151-95. DOI: 10.1017/s031716710002521x. View

Tallman J, Thomas J, Gallager D . GABAergic modulation of benzodiazepine binding site sensitivity. Nature. 1978; 274(5669):383-5. DOI: 10.1038/274383a0. View

10.

Wastek G, Speth R, Reisine T, Yamamura H . The effect of gamma-aminobutyric acid on 3H-flunitrazepam binding in rat brain. Eur J Pharmacol. 1978; 50(4):445-7. DOI: 10.1016/0014-2999(78)90152-8. View

11.

Geller H, Taylor D, Hoffer B . Benzodiazepines and central inhibitory mechanisms. Naunyn Schmiedebergs Arch Pharmacol. 1978; 304(2):81-8. DOI: 10.1007/BF00495542. View

12.

Paul S, Skolnick P . Rapid changes in brain benzodiazepine receptors after experimental seizures. Science. 1978; 202(4370):892-4. DOI: 10.1126/science.715447. View

13.

Briley M, Langer S . Influence of GABA receptor agonists and antagonists on the binding of 3H-diazepam to the benzodiazepine receptor. Eur J Pharmacol. 1978; 52(1):129-32. DOI: 10.1016/0014-2999(78)90031-6. View

14.

Martin I, Candy J . Facilitation of benzodiazepine binding by sodium chloride and GABA. Neuropharmacology. 1978; 17(11):993-8. DOI: 10.1016/0028-3908(78)90145-4. View

15.

Tallman J, Paul S, Skolnick P, Gallager D . Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science. 1980; 207(4428):274-81. DOI: 10.1126/science.6101294. View

16.

Soubrie P, Thiebot M, Jobert A, Montastruc J, Hery F, Hamon M . Decreased convulsant potency of picrotoxin and pentetrazol and enhanced [3H]flunitrazepam cortical binding following stressful manipulations in rats. Brain Res. 1980; 189(2):505-17. DOI: 10.1016/0006-8993(80)90109-2. View

17.

Perkins M, Stone T . Blockade of striatal neurone responses to morphine by aminophylline: evidence for adenosine mediation of opiate action. Br J Pharmacol. 1980; 69(1):131-7. PMC: 2044179. DOI: 10.1111/j.1476-5381.1980.tb10892.x. View

18.

Karobath M, DREXLER G, Supavilai P . Modulation by picrotoxin and IPTBO of 3H-flunitrazepam binding to the GABA/benzodiazepine receptor complex of rat cerebellum. Life Sci. 1981; 28(3):307-13. DOI: 10.1016/0024-3205(81)90738-4. View

19.

Perkins M, Bowery N, Hill D, Stone T . Neuronal responses to ethylenediamine: preferential blockade by bicuculline. Neurosci Lett. 1981; 23(3):325-7. DOI: 10.1016/0304-3940(81)90019-7. View

20.

Lloyd H, Perkins M, Gaitonde M, Stone T . Uptake and calcium-dependent release of ethylenediamine (1,2-diaminoethane) by rat brain slices. J Neurochem. 1982; 38(4):1118-22. DOI: 10.1111/j.1471-4159.1982.tb05356.x. View