Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thermoregulation is a complex intercommunicative function requiring coordination between core body temperature (CBT), the central nervous system, and peripheral vasculature. In menopausal women, dysregulation of thermoregulatory mechanisms leads to hot flushes and night sweats. A previous study in ovariectomized (OVX) rats has suggested that mirtazapine can alleviate thermoregulatory dysfunction by blocking 5-HT(2A) receptor signaling. This is in opposition to other work in which 5-HT(2A) receptor blockade appeared to exacerbate thermoregulatory dysfunction in OVX rats. Thus, the goals of the present study were to reexamine the effects of mirtazapine on temperature regulation in OVX rat models and explore further the role of 5-HT(2A) receptor blockade. Mirtazapine exhibited potent functional antagonism (EC(50)=0.62 nM) at the cloned human 5-HT(2A) receptor. In the morphine-dependent model of thermoregulatory dysfunction, mirtazapine (10 mg/kg, i.p.) induced an increase in tail-skin temperature (TST) prior to naloxone administration. In the telemetry model, mirtazapine (0.3-3 mg/kg, i.p.) caused an increase in TST. However, at the highest dose tested (10 mg/kg, i.p.), mirtazapine induced a small but significant decrease in TST followed by an increase in TST. To examine this finding further, mirtazapine's effect on CBT was determined. Administration of mirtazapine (1-3 mg/kg, i.p.) resulted in a slight decrease in CBT but at the 10 mg/kg dose a dramatic decrease (-3.6 degrees C) in CBT was observed. These data support the concept that 5-HT(2A) receptors play a role in temperature regulation but that functional blockade of these receptors by mirtazapine is not a likely mechanism for restoring thermoregulatory processes in OVX rats.
 ...
PMID:Effects of the 5-HT2A antagonist mirtazapine in rat models of thermoregulation. 1706 60

The purposes of the study are to evaluate the efficacy and safety of mirtazapine 30 mg/daily for 12 weeks to reduce hot flushes (HF) in women with previous breast cancer and to assess the influence of the same treatment on sleep quality and other menopausal symptoms. A prospective pilot trial was conducted in 40 breast cancer patients with at least seven HF per day. A HF diary was completed daily; sleep quality and other menopausal symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI), the Menopause Rating Scale (MRS) and the SF-36 Health Survey. Treatment was never started by 13 out of 40 patients (32.5%) and was interrupted by 7 out of 27 patients (25%) due to of the occurrence of side effects (mostly somnolence). In the remaining 20 patients who completed the three months treatment period, there was a 55.6% (p < 0.05) reduction in HF frequency and 61.9% (p < 0.05) reduction in HF score as compared to baseline. A significant reduction in the MRS score (32.8%; p < 0.05) was observed. Mirtazapine appears to be effective in reducing HF in breast cancer survivors. The more frequent side effect was somnolence. A sizeable compiliance problem has been observed due to the reluctance to take antidepressant drugs and to side effects.
 ...
PMID:Mirtazapine for the treatment of hot flushes in breast cancer survivors: a prospective pilot trial. 1776 Jun 71