Chlormethiazole Attenuates the Derangement of Sensory Evoked Potential (SEP) Induced by ICV Administration of NMDA

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1993 Jan 1

PMID 7870961

Citations 2

Authors

P Thoren

M Sjolander

Affiliations

Soon will be listed here.

Abstract

Administration to anaesthetized rats of N-methyl-D-aspartate (NMDA 30 nmol ICV) induced a profound derangement of stimulation evoked potential (f-SEP) and also autonomic excitation with an increase in arterial blood pressure and heart rate. These effects were antagonised by pretreatment with dizocilpine (0.5 mg/kg IV). Pretreatment with chlormethiazole (20 mg/kg IV 26 min before NMDA) also markedly diminished the derangement of f-SEP. At the end of the registration period 2 h after NMDA the SEP had recovered to 72.7 +/- 3.4 (% of control; mean +/- SEM) in saline-treated rats as compared to 96.1 +/- 5.6% in chlormethiazole treated animals (P < 0.01). In contrast to dizocilpine, chlormethiazole alone had no effect on heart rate or blood pressure and did not alter the autonomic effects of ICV NMDA. These results demonstrate that chlormethiazole can antagonise some NMDA-receptor mediated functions, even though there is no evidence that it is an NMDA antagonist.

Citing Articles

Chlormethiazole antagonises seizures induced by N-methyl-DL-aspartate without interacting with the NMDA receptor complex.

Cross A, Snape M, Green A Psychopharmacology (Berl). 1993; 112(4):403-6.

PMID: 7871049 DOI: 10.1007/BF02244886.

A study of the mechanism of MDMA ('ecstasy')-induced neurotoxicity of 5-HT neurones using chlormethiazole, dizocilpine and other protective compounds.

Colado M, Green A Br J Pharmacol. 1994; 111(1):131-6.

PMID: 7516800 PMC: 1910050. DOI: 10.1111/j.1476-5381.1994.tb14034.x.

References

Cross A, Jones J, Baldwin H, Green A . Neuroprotective activity of chlormethiazole following transient forebrain ischaemia in the gerbil. Br J Pharmacol. 1991; 104(2):406-11. PMC: 1908555. DOI: 10.1111/j.1476-5381.1991.tb12443.x. View

Hajos M, Engberg G . A role of excitatory amino acids in the activation of locus coeruleus neurons following cutaneous thermal stimuli. Brain Res. 1990; 521(1-2):325-8. DOI: 10.1016/0006-8993(90)91560-4. View

Cross A, Stirling J, Robinson T, Bowen D, Francis P, Green A . The modulation by chlormethiazole of the GABAA-receptor complex in rat brain. Br J Pharmacol. 1989; 98(1):284-90. PMC: 1854653. DOI: 10.1111/j.1476-5381.1989.tb16893.x. View

Gill R, Kemp J . Protection of CA1 pyramidal cell function by MK-801 following ischaemia in the gerbil. Neurosci Lett. 1989; 105(1-2):101-6. DOI: 10.1016/0304-3940(89)90019-0. View

Sonsalla P, Nicklas W, Heikkila R . Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity. Science. 1989; 243(4889):398-400. DOI: 10.1126/science.2563176. View

Ennis M, Aston-Jones G . Activation of locus coeruleus from nucleus paragigantocellularis: a new excitatory amino acid pathway in brain. J Neurosci. 1988; 8(10):3644-57. PMC: 6569606. View

Buchan A, Slivka A, Xue D . The effect of the NMDA receptor antagonist MK-801 on cerebral blood flow and infarct volume in experimental focal stroke. Brain Res. 1992; 574(1-2):171-7. DOI: 10.1016/0006-8993(92)90814-p. View

Addae J, Stone T . Effects of anticonvulsants on responses to excitatory amino acids applied topically to rat cerebral cortex. Gen Pharmacol. 1988; 19(3):455-62. DOI: 10.1016/0306-3623(88)90047-x. View

Talman W, Granata A, Reis D . Glutamatergic mechanisms in the nucleus tractus solitarius in blood pressure control. Fed Proc. 1984; 43(1):39-44. View

10.

Gill R, FOSTER A, Woodruff G . MK-801 is neuroprotective in gerbils when administered during the post-ischaemic period. Neuroscience. 1988; 25(3):847-55. DOI: 10.1016/0306-4522(88)90040-1. View

11.

Wong E, Kemp J, Priestley T, Knight A, Woodruff G, Iversen L . The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986; 83(18):7104-8. PMC: 386661. DOI: 10.1073/pnas.83.18.7104. View

12.

Green A, de Souza R, Williams J, Murray T, Cross A . The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole. Neuropharmacology. 1992; 31(4):315-21. DOI: 10.1016/0028-3908(92)90062-t. View

13.

Colado M, Murray T, Green A . 5-HT loss in rat brain following 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine. Br J Pharmacol. 1993; 108(3):583-9. PMC: 1908028. DOI: 10.1111/j.1476-5381.1993.tb12846.x. View

14.

MILLS E, Minson J, Pilowsky P, Chalmers J . N-methyl-D-aspartate receptors in the spinal cord mediate pressor responses to stimulation of the rostral ventrolateral medulla in the rat. Clin Exp Pharmacol Physiol. 1988; 15(2):147-55. DOI: 10.1111/j.1440-1681.1988.tb01056.x. View

15.

Harrison N, Simmonds M . Two distinct interactions of barbiturates and chlormethiazole with the GABAA receptor complex in rat cuneate nucleus in vitro. Br J Pharmacol. 1983; 80(2):387-94. PMC: 2045014. DOI: 10.1111/j.1476-5381.1983.tb10045.x. View