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Eur J Neurosci. 2003 Feb;17(3):447-54.
Endogenous and exogenous dopamine presynaptically inhibits glutamatergic reticulospinal transmission via an action of D2-receptors on N-type Ca2+ channels.
Svensson E, Wikstrom MA, Hill RH, Grillner S.
The Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
In this study, the effects of exogenously applied and endogenously released dopamine (DA), a powerful modulator of the lamprey locomotor network, are examined on excitatory glutamatergic synaptic transmission between reticulospinal axons and spinal neurons. Bath application of DA (1-50 micro m) reduced the amplitude of monosynaptic reticulospinal-evoked glutamatergic excitatory postsynaptic potentials (EPSPs). The effect of DA was blocked by the D2-receptor antagonist eticlopride, and mimicked by the selective D2-receptor agonist 2,10,11 trihydroxy-N-propyl-noraporphine hydrobromide (TNPA). Bath application of the DA reuptake blocker bupropion, which increases the extracellular level of dopamine, also reduced the monosynaptic EPSP amplitude. This effect was also blocked by the D2-receptor antagonist eticlopride. To investigate if the action of DA was exerted at the presynaptic level, the reticulospinal axon action potentials were prolonged by administering K+ channel antagonists while blocking l-type Ca2+ channels. A remaining Ca2+ component, mainly dependent on N and P/Q channels, was depressed by DA. When DA (25-50 micro m) was applied in the presence of omega-conotoxin GVIA, a toxin specific for N-type Ca2+ channels, it failed to affect the monosynaptic EPSP amplitude. DA did not affect the response to extracellularly ejected d-glutamate, the postsynaptic membrane potential, or the electrical component of the EPSPs. DA thus acts at the presynaptic level to modulate reticulospinal transmission.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12581163&dopt=Abstract
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issc.debbs.ndhg.dnd.ca
BACKGROUND: Since the addition of bupropion slow release (Zyban, GlaxoSmithKline, Mississauga) to the Department of National Defence (DND) smoking cessation program (Butt Out), utilizing bupropion (Zyban) in combination with behaviour modification counselling, the Directorate of Medical policy has received several anecdotal reports from pharmacists and Canadian Forces members attributing significant side effects to the use of Zyban. As a result, the DND wished to assess the benefits versus the risks of using Zyban as part of the smoking cessation program. Subsequently, a retrospective review of the use of Zyban within the Canadian Forces over a one-year period was solicited to assess current policies. METHODS: Surveys were sent to Canadian Forces members receiving Zyban between September 1, 1998 and August 31, 1999. Members were questioned about smoking history and current status, perceived effectiveness of bupropion and both positive and negative experiences with the drug. Those reporting side effects and who had consented were contacted for an interview to obtain further details and information regarding the use of medical resources and effects on job performance. Members of the Canadian Forces visiting a doctor due to side effects were asked for permission to review their medical charts. RESULTS: Zyban was dispensed to approximately 1171 members over the one-year period and 357 responded to the survey. The point prevalence smoking cessation rate was 47% at the time of the survey and ex-smokers had been smoke-free for a mean of 181 days. Approximately 91% of ex-smokers and 52% of smokers found Zyban helpful in quitting. Side effects were reported by 252 members and 160 interviews were completed. Forty-three interviewees had seen a doctor because of side effects. Sixteen of the 43 charts were audited. Fifty-two respondents stated that side effects affected their ability to do their primary job. Two individuals were hospitalized for a total of six days. CONCLUSIONS: In light of the demonstrated effectiveness of Zyban and the overwhelming health benefits associated with smoking cessation, it is recommended that the current policies of funding for the DND smoking cessation program be left in place. The impact of Zyban's side effects on job performance and medical resources should be minimized through close monitoring and Zyban prescriptions should be dispensed in two-week quantities.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12584579&dopt=Abstract
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partners.org
Despite the superior side effect profile of the newer antidepressants over the tricyclics and monoamine oxidase inhibitors, all newer antidepressants are associated with a wide array of side effects. Clinicians are constantly confronted with the challenge of managing these side effects in the context of minimal research to prove one management strategy is more effective than another. The purpose of this study was to examine prescribing practices regarding the management of SSRI-associated side effects in a sample of psychiatrists attending a psychopharmacology review course. A total of 439 out of 800 clinicians (55%) attending a psychopharmacology review course responded to our questionnaire that was given prior to beginning the review course, though not all respondents answered all four items on the questionnaire. Among these items were questions designed to assess clinician preference for the management of SSRI-induced side effects. As a treatment for SSRI-induced sexual dysfunction, 43% (143/330) chose adding bupropion, while 36% (120/330) opted to switch agents as their first choice; for SSRI-induced insomnia, 78% (264/326) chose adding trazodone. Switching agents was the first choice of 61% (214/353) of clinicians for managing SSRI-induced agitation, 93% (339/363) for managing SSRI-associated weight gain. In an effort to manage most SSRI-associated side effects (with the exception of sexual dysfunction and insomnia), the majority of the clinicians responding to our survey opted to switch agents rather than add a specific medication to the existing SSRI. In our opinion, this practice may reflect the relative lack of research studies on the role of adjunctive treatments in the management of SSRI-induced side effects and/or the tendency to favor monotherapy over polypharmacy.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12585563&dopt=Abstract
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