Protocols · Immune
VIP dosage protocol
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Dosage protocol
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VIP: research background
What the compound is
Vasoactive intestinal peptide (VIP) is a naturally occurring 28-amino acid neuropeptide discovered in 1970 (PMID 27786097, PMID 37742737). It is abundant in the lungs and other organs and plays roles in various biological functions, including heart contractility, vasodilation, blood pressure regulation, and neuroendocrine-immune communication (PMID 27553659, PMID 37742737). Aviptadil is a synthetic drug formulation of VIP (PMID 34846667). In some formulations, it has been combined with the adrenergic drug phentolamine (PMID 11566015).
How it is thought to work
VIP is recognized for its anti-inflammatory and immune-modulatory activities (PMID 27553659, PMID 23094826, PMID 34846667). In mammals, studies have shown it inhibits the production and action of inflammatory mediators (PMID 23094826). In the nervous system, VIP supports neuronal survival under both physiological and pathological conditions, acting as an indirect protectant primarily through glial cells. These cells produce neurotrophic factors and inhibit pro-inflammatory mediators in response to VIP (PMID 27786097). In the cerebral cortex, VIP-expressing GABAergic inhibitory interneurons (VIP-INs) are important regulators of network dynamics and circuit development (PMID 33794534).
What laboratory and animal studies report
Numerous animal studies since the late 1970s have highlighted VIP's role in the immune system and its therapeutic potential in animal models of human disease (PMID 23094826). VIP has been shown to prevent chronic cartilage damage and joint remodeling in animal models of osteoarthritis (PMID 27553659). Dysfunction of VIP-INs has been identified in animal models of genetically determined neurodevelopmental disorders, potentially influencing pathogenesis of conditions like autism spectrum disorder and intellectual disability (PMID 33794534).
Human evidence and regulatory status so far
Aviptadil was approved in New Zealand by April 2000 for erectile dysfunction (ED) (PMID 11566015). It was granted Orphan Drug Designation by the US FDA in 2001 for acute respiratory distress syndrome (ARDS) and in 2005 for pulmonary arterial hypertension (PMID 34846667). Investigational New Drug (IND) licenses for human trials of Aviptadil were issued by both the US FDA and the European Medicines Agency (EMEA) (PMID 34846667). In July 2000, the FDA allowed human studies in the US for limited durations (3 months) and dosing frequency (not exceeding three doses per week) (PMID 11566015). Preliminary clinical trials appear to support Aviptadil's benefit in COVID-19 patients, but further adequate clinical trials are needed (PMID 34846667).
Open questions and limitations
Contradictory reports exist regarding VIP's role in osteoarthritis; while some evidence suggests down-regulation of VIP contributes to the disease, other studies indicate VIP accumulation in joints can also contribute to OA (PMID 27553659). The carcinogenicity observed in animal models for phentolamine mesylate, a component of some aviptadil formulations, was deemed irrelevant to human carcinogenic risk by an independent review in March 2000 (PMID 11566015). The FDA, however, recommended a two-year rodent study for aviptadil due to previously reported brown adipose tissue findings (PMID 11566015). General limitations for VIP as a medication include the need for extended-release formulations and VIP analogues to improve its therapeutic potential (PMID 37742737).
Studies cited in this section
- Aviptadil (Senatek). — Current opinion in investigational drugs (London, England : 2000), 2001 (PMID 11566015)
- Editorial: vasoactive intestinal peptide (vip): historic perspective and future potential. — Endocrine, metabolic & immune disorders drug targets, 2012 (PMID 23094826)
- A Role for Vasoactive Intestinal Peptide Interneurons in Neurodevelopmental Disorders. — Developmental neuroscience, 2021 (PMID 33794534)
- Role of vasoactive intestinal peptide in osteoarthritis. — Journal of biomedical science, 2016 (PMID 27553659)
- The effects of vasoactive intestinal peptide in neurodegenerative disorders. — Neurological research, 2017 (PMID 27786097)
- The role of vasoactive intestinal peptide in pulmonary diseases. — Life sciences, 2023 (PMID 37742737)
- Anticipated pharmacological role of Aviptadil on COVID-19. — Environmental science and pollution research international, 2022 (PMID 34846667)
Summarised from the PubMed abstracts listed above. Educational reference only — not medical advice or instructions.
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