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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Collingridge, G. L. Coan, E. J. |
| Abstract | The effects of representative drugs from three classes of psychotomimetic compounds (arylcyclohexylamines, benzomorphan opioids and dioxolanes) have been examined on synaptic transmission at an identified monosynaptic pathway in rat hippocampal slices. The compounds tested were phencyclidine (PCP) and ketamine, the racemate and isomers of SKF 10,047 (N-allylnormetazocine), and the isomers of dioxadrol (dexoxadrol and levoxadrol). In the absence of added magnesium ions (Mg) in the perfusion medium low frequency stimulation of the Schaffer collateral-commissural pathway evoked a burst of population spikes in the CA1 cell body region. The secondary components of this response could be abolished by the selective N-methyl-D-aspartate (NMDA) antagonist D-2-amino-5-phosphonovalerate (APV). PCP (1 microM) or ketamine (10 microM) selectively blocked the secondary components of the synaptic response. The effect of PCP was neither mimicked nor prevented by hexamethonium and atropine, phentolamine and propranolol, or clonidine and was therefore unlikely to involve cholinergic or adrenergic neurotransmitter systems. The sigma opiate, (+/-)-SKF 10,047 (10 microM) also abolished selectively the secondary components of the synaptic response. There was no apparent difference between the potency of the stereoisomers of this compound. The action of (+/-)-SKF 10,047 was not affected by either naloxone or haloperidol, indicating that this effect did not involve opioid receptors or the haloperidol-sensitive sigma site. Dexoxadrol (10 microM), but not levoxadrol (10 microM), also selectively blocked the secondary components of the synaptic response. It is concluded that these psychotomimetic agents can block an NMDA receptor-mediated component of synaptic transmission in the hippocampus and that this effect is mediated by a specific PCP/sigma site. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 91 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1987-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Hallucinogens Pharmacology Hippocampus Physiology Phenazocine Analogs & Derivatives Phencyclidine Receptors, Neurotransmitter Synapses Analgesics Animals Dioxolanes Drug Effects In Vitro Techniques Ketamine Kinetics Magnesium Neuromuscular Depolarizing Agents Piperidines Receptors, N-Methyl-D-Aspartate Synaptic Transmission Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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