Clinical neuropharmacology
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Clin Neuropharmacol · Jan 1993
Review Comparative StudyNovel serotonergic mechanisms and clinical experience with nefazodone.
Chronic administration of antidepressant drugs enhances synaptic serotonergic transmission. Nefazodone, a member of a new class of antidepressants, has a pharmacologic profile that is distinct from the first-generation agents (e.g., tricyclics and monoamine oxidase inhibitors) as well as the more selectively acting second-generation agents (e.g., serotonin or norepinephrine uptake inhibitors, and serotonin type 1A partial agonists). Nefazodone acts both as a 5-HT2 receptor antagonist and as a serotonin (5-HT) reuptake inhibitor. ⋯ In placebo-controlled studies comparing nefazodone and the tricyclic antidepressant imipramine, the drugs produced comparable and significant therapeutic benefit. Nefazodone is associated with fewer adverse events than imipramine. Nefazodone lacks the troublesome anticholinergic side effects of tricyclic antidepressants, as well as serotonergic/noradrenergic-mediated effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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Clin Neuropharmacol · Jan 1993
ReviewSerotonin receptor subtypes in depression: evidence from studies in neuroendocrine regulation.
Serotonin (5-HT) neuroendocrine tests are a valid and acceptable means of measuring 5-HT neurotransmission in humans. Recently, the availability of selective 5-HT receptor ligands has allowed the assessment of specific 5-HT receptor subtype function using neuroendocrine methods. ⋯ In contrast, endocrine responses to direct 5-HT1A and 5-HT2/1C receptor agonists are not consistently attenuated in depressed patients. The current data suggest that depressive illness is associated with an impairment of 5-HT neurotransmission that involves decreased 5-HT release rather than altered sensitivity of postsynaptic 5-HT receptors.
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Clin Neuropharmacol · Oct 1991
Case ReportsProlonged survival following the inadvertent intrathecal administration of vincristine: clinical and electrophysiologic analyses.
A 23-year-old man with a lymphoblastic lymphoma accidentally received 2.0 mg of vincristine intrathecally instead of intravenously. Although he underwent immediate CSF drainage, symptoms of an ascending myeloencephalopathy developed at 48 h. This progressed to coma, initially with a diffusely slow EEG, which evolved into alpha coma. ⋯ An increase in amplitude in the 10th month was accompanied by the return of some nystagmoid eye movements. The patient's lymphoma then recurred, and further treatment was not attempted. This tragic case, in which transient exposure to a microtubular poison produced severe CNS toxicity, allows some insights into the mechanisms of alpha coma.
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Clin Neuropharmacol · Jun 1991
Multicenter Study Clinical TrialAn open multicenter trial of Sinemet CR in levodopa-naive Parkinson's disease patients.
It has been proposed that initiation of anti-Parkinson therapy with continuous release formulations of Sinemet might prevent or delay the development of adverse effects associated with chronic levodopa therapy employed in standard formulations. In anticipation of a prospective study comparing Sinemet to Sinemet CR in previously untreated Parkinson's disease patients, we evaluated Sinemet CR as primary therapy in 45 levodopa-naive Parkinson's disease patients in a 12 week, open-label, multi-center study. At the conclusion of the study, optimal results were obtained with levodopa administered as Sinemet CR in a total daily dose of 497 mg divided into 2.4 doses per day. ⋯ Statistically significant improvement was also noted in total disability as well as in each of its components. Adverse experiences were mild and transient and no significant laboratory abnormalities were encountered. We conclude that a daily dose of 1 to 1.5 tablets b.i.d. of Sinemet CR as primary therapy for patients with Parkinson's disease is well tolerated and provides effective therapy.
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The body has an endogenous analgesic system that prevents excess pain from interfering with the normal body functions. Depression of pain sensations occurs within the dorsal horn of the spinal cord where the primary pain fibers, which transmit pain sensations from the periphery, synapse with neurons that transmit pain to the higher centers. There appear to be two mechanisms by which the transmission of pain sensations are depressed; these include hyperpolarization of interneurons within the dorsal cord and depressing the release of the neurotransmitters associated with pain transmission. ⋯ Opiate drugs, such as morphine, interact with opioid receptors and produce analgesia by the same mechanisms as enkephalin, i.e., hyperpolarization of interneurons and depressing the release of transmitters associated with transmission of pain. In addition, morphine can interact with opioid receptors located in the supraspinal structures and activate the supraspinal system. Adrenergic drugs that interact with specific receptors also produce analgesia and it has been suggested that morphine interacts with the adrenergic system to produce analgesia.