Drugs online research references
J Neurophysiol. 2002 May;87(5):2324-36.
Interaction of dopamine D1 and NMDA receptors mediates acute clozapine potentiation of glutamate EPSPs in rat prefrontal cortex.
Chen L, Yang CR.
Neuroscience Discovery, Eli Lilly and Co., Indianapolis, Indiana 46285-0510, USA.
The atypical antipsychotic drug clozapine effectively alleviates both negative and positive symptoms of schizophrenia via unclear cellular mechanisms. Clozapine may modulate both glutamatergic and dopaminergic transmission in the prefrontal cortex (PFC) to achieve part of its therapeutic actions. Using whole cell patch-clamp techniques, current-clamp recordings in layers V-VI pyramidal neurons from rat PFC slices showed that stimulation of local afferents (in 2 microM bicuculline) evoked mixed [AMPA/kainate and N-methyl-D-aspartate (NMDA) receptors] glutamate receptor-mediated excitatory postsynaptic potentials (EPSPs). Clozapine (1 microM) potentiated polysynaptically mediated evoked EPSPs (V(Hold) = -65 mV), or reversed EPSPs (rEPSP, V(Hold) = +20 mV) for >30 min. The potentiated EPSPs or rEPSPs were attenuated by elevating [Ca(2+)](O) (7 mM), by application of NMDA receptor antagonist 2-amino5-phosphonovaleric acid (50 microM), or by pretreatment with dopamine D1/D5 receptor antagonist SCH23390 (1 microM) but could be further enhanced by a dopamine reuptake inhibitor bupropion (1 microM). Clozapine had no significant effect on pharmacologically isolated evoked NMDA-rEPSP or AMPA-rEPSPs but increased spontaneous EPSPs without changing the steady-state resting membrane potential. Under voltage clamp, clozapine (1 microM) enhanced the frequency, and the number of low-amplitude (5-10 pA) AMPA receptor-mediated spontaneous EPSCs, while there was no such changes with the mini-EPSCs (in 1 microM TTX). Taken together these data suggest that acute clozapine can increase spike-dependent presynaptic release of glutamate and dopamine. The glutamate stimulates distal dendritic AMPA receptors to increase spontaneous EPSCs and enabled a voltage-dependent activation of neuronal NMDA receptors. The dopamine released stimulates postsynaptic D1 receptor to modulate a lasting potentiation of the NMDA receptor component of the glutamatergic synaptic responses in the PFC neuronal network. This sequence of early synaptic events induced by acute clozapine may comprise part of the activity that leads to later cognitive improvement in schizophrenia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11976371&dopt=Abstract
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Br J Community Nurs. 2002 Apr;7(4):202-5.
Pharmacological management of smoking cessation.
Percival J, Milner D.
Royal College of Nursing, London.
There is evidence that pharmacological management of smoking cessation, together with advice and support, is very cost-effective and increases success rates of quit attempts. Community nurses are in a good position to intervene with smokers. All nicotine replacement therapy products are now on the Nurse Prescribers' Formulary. This article covers the scientific evidence, the guidelines on smoking cessation and the role of the health professional. Treatment options are described and useful contacts for further information are provided.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11979199&dopt=Abstract
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ohsu.edu
BACKGROUND: Recent data suggest that women smokers respond differently than men to cessation pharmacotherapies, particularly nicotine replacement therapy (NRT). Lower abstinence and higher relapse rates are often reported for women treated with NRT. Gender effects for those treated with non-nicotinic, bupropion-hydrochloride sustained release for relapse prevention have not been studied. METHODS: Data from a multicenter relapse-prevention (RP) trial of bupropion (November 1995-June 1998) were analyzed for gender differences. Men and women smokers (N=784) were treated with open-label bupropion for 7 weeks. Those abstinent at Week 7 (n=432) were enrolled in the double-blind relapse-prevention phase and randomized to placebo or continued bupropion for 45 additional weeks. RESULTS: Differences in point-prevalence abstinence rates between men (61.8%) and women (55.6%) in open-label bupropion (Week 7) were not significant. In the RP-phase Week 52, continuous abstinence rates for men and women were 37.8% and 36.4% (bupropion) and 36.6% and 29.9% (placebo), respectively; point-prevalence abstinence rates for men and women were 54.1% and 55.9% (bupropion) and 42.9% and 41.3% (placebo), respectively. Abstinence rates and time to relapse were superior for both men and women who received longer treatment. Gender differences within treatment groups were not significant. Median time to relapse was equal for men and women within each treatment group: Week 32 for bupropion and Week 20 for placebo. CONCLUSIONS: Our data suggest that bupropion is a promising pharmacotherapy for preventing relapse, particularly for women.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11988379&dopt=Abstract
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