Loxicodegol

Loxicodegol Uses, Dosage, Side Effects, Food Interaction and all others data.

Loxicodegol was developed by Nektar Therapeutics as an opioid analgesic with low abuse potential for the treatment of chronic pain . The lack of abuse potential is believed to be due to the drug's slow rate of entry into brain, a unique characteristic compared to others in the opioid class . This is also thought to be the reason behind the reduced frequency of CNS-mediated adverse effects, like sedation, seen with Loxicodegol. Nektar Therapeutics has filed an application for FDA approval of Loxicodegol for use in the treatment of chronic lower back pain

Loxicodegol displays full analgesic activity comparable to that of oxycodone, producing similar acetone-writhing test responses in mice and hot-plate test maximal latencies in rats .

The safety profile of Loxicodegol is much improved from that of other opioid analgesics . The incidence of respiratory depression and sedation is reduced compared to oxycodone and morphine. Generalized pruritus occurred in 7.3% and 4.9% of subjects at 200mg and 400mg of Loxicodegol compared to 41.5% with 40mg oxycodone. Nausea occurred in 2.5%, 2.4%, and 7.3% with 100mg, 200mg, and 400mg of Loxecodegol compared to 29.3% with 40mg oxycodone. Lastly, vomiting occurred in 2.4% with both 200mg and 400mg Loxicodegol compared to 24.4% with 40mg oxycodone.

Loxicodegol
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Loxicodegol
Generic	Loxicodegol
Type
Formula	C₃₁H₄₉NO₁₀
Weight	Average: 595.73 Monoisotopic: 595.335646782
Groups	Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Loxicodegol was developed as an opioid analgesic with low abuse potential for use in treating chronic pain . An application has been filed for FDA approval of Loxicodegol for use in treating chronic lower back pain.

How Loxicodegol works

Loxicodegol is a full agonist at the μ-opioid receptor. It also displays selectivity towards this subtype with an affinity of 237 nM compared to 4150 nM and >100000 nM for the δ- and κ-opioid receptors. The μ-opioid receptor is activated with an EC₅₀ of 12.5 μM. Activation of this receptor produces an inhibitory effect on neurotransmission through Gi/Go coupling . Opioid medications like Loxicodegol inhibit voltage gated Ca²⁺ channel opening presynaptically on C fibres and activate inward-rectifying K⁺ channels post-synaptically on 2nd order neurons, leading to hyperpolarization. Together, these prevent the nociceptive signal from traveling up the spinal cord to the brain. In the brain, opioids work through a mechanism of inhibition of inhibition to allow regulatory neurons to suppress nociception.

Volume of Distribution

Loxicodegol has a steady-state Vd of 4.19 L/kg .

Elimination Route

Loxicodegol has a Tmax of 1.8h and a bioavailability of 34% with oral administration . It enters the brain about 17-70 times more slowly than oxycodone . Loxicodegol is also a p-glycoprotein substrate further reducing its transport into the brain.