News in brief: Clues to designer tricyclic antidepressants in neuropathic pain; Rethink your MRI imaging to cut carbon footprint; Monash team trials treatment for bvFTD

11 May 2022

Clues to designer tricyclic antidepressants in neuropathic pain

Australian research has provided evidence for the off-label prescription of tricyclic antidepressants (TCAs) for neuropathic pain.

An experimental study comprising 11 TCAs and two related drugs evaluated by calcium influx assays showed all drugs demonstrated moderate inhibition of the hCaV2.2 channel.

“Further, tricyclic structures predominantly consisting of a carbon framework and bearing a flexible amine sidechain tended to show slightly stronger inhibition, and secondary amines were preferred over tertiary.”

The study also noted that halogen substitution appeared to improve potency.

“All of these findings provide valuable insights into how more effective CaV2.2 inhibitors based on the TCA structure might be developed.”

Read more in RSC Medicinal Chemistry

Rethink your MRI imaging to cut carbon footprint

Clinicians can help reduce the healthcare carbon footprint by adopting a three-pronged strategy to make more efficient use of diagnostic imaging, according to Australian researchers.

Diagnostic imaging and pathology testing account for almost 10% of the hospital carbon footprint, with MRI and CT scans accounting for a high proportion of it, a Melbourne University study found.

The carbon emissions from an MRI are equivalent to driving a car for 145 km, while a CT scan carbon emission is equal to driving 76 km, the findings in Lancet Regional Health showed.

Much of the large carbon footprint was due to electricity use by scanners, and in particular, their standby power use, said the researchers, who recommended that clinicians and administrators make efforts to reduce unnecessary imaging and/or switch imaging to a lower carbon modality such as X-rays.

Other carbon footprint reduction tips include turning scanners off when they are not required rather than leaving them on standby and ensuring existing scanners have high utilisation rates, they suggested.

Monash team trials treatment for bvFTD

Sodium selenate shows promise as disease-modifying treatment for patients with behavioural variant frontotemporal dementia (bvFTD), according to Monash University researchers.

Preliminary results show it may stabilise what would normally be escalating behavioural issues, and promote slowing of brain shrinkage due to the disease.

A phase 1 trial run in conjunction with the Royal Melbourne Hospital, showed that the drug, which increases tau dephosphorylation through protein phosphatase 2 activation, was safe and well-tolerated in 12 patients with bvFTD over a period of 12 months.

Most patients receiving sodium selenate showed no change in their cognitive or behavioural symptoms, and reduced rates of brain atrophy over the trial period.

Small declines in MRI and cognitive and behavioural measures were observed over the treatment period, and there was no evidence for change in CSF protein levels (t-tau, p-tau, or NfL).

The researchers led by Dr Lucy Vivash, from Monash University’s Department of Neuroscience, noted there were two distinct groups when measuring disease progression markers over the course of the study: one (n = 4) with substantial brain atrophy (2.5% to 6.5% reduction) and cognitive and behavioural decline over the 12-month treatment period. The second group (n = 7) had no detectable change in cognitive and behavioural measures and less brain atrophy (0.3% to 1.7% reduction).

“We have previously shown, in a Phase 2 trial, that sodium selenate given to patients with mild to moderate Alzheimer’s Disease resulted in less neurodegeneration than in those who did not,” said Dr Vivash.

Importantly those patients in the trial with higher levels of selenium, a breakdown product of sodium selenate, in their bloodstream showed less cognitive decline, she noted.

The results from the trial have been published in the journal Alzheimer’s and Dementia: Translational Research and Clinical Interventions.

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