Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of i.v. administered flumazenil (3.0 mg) were studied in healthy male subjects who received pretreatment with p.o. placebo or lorazepam. The duration of placebo or lorazepam (3.0 mg single p.o. daily dose) pretreatment before a flumazenil or placebo injection was 1, 3, 7 or 14 days in four sequential groups of subjects. Initial administration of lorazepam produced a classic sedative profile of effects on various psychomotor/behavioral performance, observer-rated and subject-rated measures. Tolerance to repeated daily administration of lorazepam was suggested by a progressive diminution of performance disrupting effects. In subjects pretreated with placebo, flumazenil increased subject-ratings of dizziness over preinjection ratings. Flumazenil produced an immediate reversal of lorazepam effects in subjects who were not tolerant to lorazepam (1- and 3-day pretreatment groups). Flumazenil did not precipitate withdrawal symptoms in subjects who received a single administration of lorazepam. Precipitated withdrawal symptoms were evident after 3 and 7 days of lorazepam pretreatment, and there was a tendency toward precipitated withdrawal symptoms (that included one panic attack) after 14 days of lorazepam pretreatment. Precipitated withdrawal was characterized by an elevation in subject-rated symptoms including dizziness, tenseness, tachycardia, perceptual disturbance and sweating. Symptoms were maximal immediately after injection, usually mild in severity and usually resolved within 1 hr. There was no evidence of precipitated withdrawal on psychomotor/behavioral performance or observer ratings. The present study provides the strongest human experimental evidence to date that flumazenil can precipitate withdrawal symptoms after a history of repeated benzodiazepine exposure.
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PMID:Intravenous flumazenil following acute and repeated exposure to lorazepam in healthy volunteers: antagonism and precipitated withdrawal. 851 1

Major depressive disorder (MDD) is a common, serious, debilitating condition affecting 350 million people worldwide, which remains to be unsatisfactorily treated with 53% of patients still complaining of symptoms after completing their courses with the correct dosage. Ketamine, which was approved by the Food and Drug Administration in 2019, is a potential treatment option for those recalcitrant cases. The mechanism of ketamine is not fully understood, but as type it is classified as an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, and can be given intravenously, intranasally and orally. It is used to treat treatment-resistant depression, depression associated with suicidal ideation, mood and anxiety disorders and depressions associated with either type of bipolar disorder. Although ketamine is considered relatively safe, several side effects have been reported with the major ones being psychiatric in the form of worsening mood, anxiety and agitation; psychotomimetic in the form of dissociation, perceptual disturbance and abnormal sensations; cardiovascular in the form of increased blood pressure and increased heart rate; and neurological in the form of headache and dizziness. Ketamine is still not approved worldwide for usage in patients with treatment-resistant MDD, but if it is approved sometime in the future with relatively fewer side effects, it is expected to significantly save millions of dollars spent yearly on patients with treatment-resistant depression and that will lift this major burden off the shoulders of healthcare professionals. This study was designed to measure the effects of ketamine, an NMDA receptor antagonist, on patients with treatment-resistant MDD and to analyse the concept that makes it different and relatively safer than other major antidepressants like selective serotonin reuptake inhibitors, monoamine oxidase inhibitors and TCAs (tricyclic antidepressants).
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PMID:Could ketamine be the answer to treating treatment-resistant major depressive disorder? 3287 73