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Mechanistic studies of the discrimin...

Sun, Wen Lin.

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Mechanistic studies of the discriminative stimulus properties of dextromethorphan and metabolites.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Mechanistic studies of the discriminative stimulus properties of dextromethorphan and metabolites./
Author:	Sun, Wen Lin.
Description:	211 p.
Notes:	Source: Dissertation Abstracts International, Volume: 61-12, Section: B, page: 6413.
Contained By:	Dissertation Abstracts International61-12B.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9997566
ISBN:	9780493051901

Mechanistic studies of the discriminative stimulus properties of dextromethorphan and metabolites.
Sun, Wen Lin.

Mechanistic studies of the discriminative stimulus properties of dextromethorphan and metabolites. - 211 p.

Source: Dissertation Abstracts International, Volume: 61-12, Section: B, page: 6413.

Thesis (Ph.D.)--University of Arkansas for Medical Sciences, 2000.

Dextromethorphan is an antitussive drug that is also subject to abuse. The receptor mechanisms that mediate the subjective effects abusers seek are unknown. These experiments characterized the discriminative stimulus properties of dextromethorphan and its major metabolite, dextrorphan, in rats to investigate the mechanisms that are responsible for its abusive effects. Dark Agouti rats were trained to discriminate dextromethorphan (18 mg/kg, i.p.) or dextrorphan (32 or 42 mg/kg, i.p.) from saline. This strain lacks CYP2D1, a homologue of human CYP2D6 that is responsible for O-demethylating dextromethorphan to form dextrorphan enabling the separation of the effects of dextromethorphan and dextrorphan. Phencyclidine-related drugs including (+)-MK-801, TCP, PCP, ketamine, dexoxadrol and (+)-NANM completely substituted for both training drugs. 3-Methoxy-morphinan, d-pentazocine, caramiphen and several other classes of abused drugs did not. The binding affinities for NMDA receptor channels of the drugs that substituted for DXM and DR were determined from the brain membranes of female dark Agouti rats in competition binding assays. These binding affinities correlated with their potencies in producing either dextromethorphan-like or dextrorphan-like responding. These results suggest that blockade of NMDA receptor channels is a common mechanism mediating the stimulus effects of dextromethorphan, dextrorphan and phencyclidine.

ISBN: 9780493051901Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Mechanistic studies of the discriminative stimulus properties of dextromethorphan and metabolites.
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520 $a Dextromethorphan is an antitussive drug that is also subject to abuse. The receptor mechanisms that mediate the subjective effects abusers seek are unknown. These experiments characterized the discriminative stimulus properties of dextromethorphan and its major metabolite, dextrorphan, in rats to investigate the mechanisms that are responsible for its abusive effects. Dark Agouti rats were trained to discriminate dextromethorphan (18 mg/kg, i.p.) or dextrorphan (32 or 42 mg/kg, i.p.) from saline. This strain lacks CYP2D1, a homologue of human CYP2D6 that is responsible for O-demethylating dextromethorphan to form dextrorphan enabling the separation of the effects of dextromethorphan and dextrorphan. Phencyclidine-related drugs including (+)-MK-801, TCP, PCP, ketamine, dexoxadrol and (+)-NANM completely substituted for both training drugs. 3-Methoxy-morphinan, d-pentazocine, caramiphen and several other classes of abused drugs did not. The binding affinities for NMDA receptor channels of the drugs that substituted for DXM and DR were determined from the brain membranes of female dark Agouti rats in competition binding assays. These binding affinities correlated with their potencies in producing either dextromethorphan-like or dextrorphan-like responding. These results suggest that blockade of NMDA receptor channels is a common mechanism mediating the stimulus effects of dextromethorphan, dextrorphan and phencyclidine.
520 $a Two groups of Sprague-Dawley rats were trained to discriminate either dextromethorphan (18/mg/kg, i.p.) or dextrorphan (32 mg/kg, i.p.) from saline. This strain has normal CYP2D1 activity. Again, phencyclidine-like drugs completely substituted for both dextromethorphan and dextrorphan. The potencies of these drugs in producing either dextromethorphan-like or dextrorphan-like responding also correlated with their binding affinities for NMDA receptor channels reported in the literature. Dextromethorphan was equipotent or more potent than dextrorphan. These results indicate that dextromethorphan is mainly responsible for the stimulus properties after its administration and suggest that the effects sought by abusers are similar to those of phencyclidine and that blockade of NMDA receptor channels is the receptor mechanism for these effects.
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