New Anti-Tinnitus Drugs May Target Vasoactive Intestinal Peptide (VIP) Excitability

Pharmacologic agents targeting vasoactive intestinal peptide (VIP) excitability represent an intriguing new therapeutic approach to the treatment of tinnitus…

The following information was obtained from a preprint titled, “Increased Pyramidal and VIP Neuronal Excitability in Primary Auditory Cortex Directly Correlates with Tinnitus Behavior”, that was recently posted on bioRxiv, an online archive and distribution service for unpublished preprints (draft manuscripts that have not yet been peer reviewed).

The paper was uploaded on November 23, 2022. Here is a link to the full text article:

This is a draft article and a developing topic. For now, here are some key passages from the paper (emphasis ours):

Tinnitus-related A1 changes were similar to findings in studies of neuropathic pain in somatosensory cortex suggesting a common pathology of these troublesome perceptual impairments. Improved understanding between excitatory, inhibitory and disinhibitory sensory cortical circuits can serve as a model for testing therapeutic approaches to the treatment of tinnitus and chronic pain.

In conclusion, in an established tinnitus model, the present study describes tinnitus-related pre- and postsynaptic changes in the physiology of A1 layer 5 pyramidal and VIP neurons from ET animals but not from ENT rat A1. Tinnitus-related increases in excitability of layer 5 PNs was accompanied by increased excitability of VIP interneurons. Future studies will examine tinnitus-related changes in PV and SOM inhibitory interneurons while considering pharmacologic agents targeting VIP excitability.

This research relates to another project involving nicotinic acetylcholine receptor modulators. (To be continued…)

This is an early access draft

This unfinished article is sent to email subscribers — but the rest of this article is underway, and aims to describe the current status of drugs that target VIP excitability (e.g. small molecule antagonists of VIP), how they relate to the path towards a treatment for tinnitus, and will include a research roundup showing where this new drug development “is at” right now (think “repurposing”?) — plus, what all this means for the possibility of targeting VIP as a treatment for tinnitus, like this new preprint talks about.

For updates on this new and emerging tinnitus treatment-related topic, remember to sign up to the Tinnitus Treatment Report email newsletter. (It’s free and you can unsubscribe with one click. No ads, no affiliate links, no nonsense.)

Meanwhile, anyone who prefers to get a head start on the follow-up article can begin by sinking their teeth into these papers:

Identification and optimization of small molecule antagonists of vasoactive intestinal peptide receptor-1 (VIPR1)

A Molecular Dynamics Study of Vasoactive Intestinal Peptide Receptor 1 and the Basis of Its Therapeutic Antagonism

Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide (Part 2): biology and clinical importance in central nervous system and inflammatory disorders

Longitudinal imaging of VIP interneurons reveals sup-population specic effects of stroke that can be rescued with chemogenetic therapy

To be continued, indeed!

Last updated: November 29, 2022 at 7:36am ET

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