Z160, an oral state-dependent, selective N-type Calcium Channel Blocker

Z160 is a first in class, oral, state dependent, selective N-type calcium channel (Cav 2.2) blocker. Z160 has demonstrated efficacy in multiple animal models of neuropathic and inflammatory pain, suggesting that Z160 has the potential to treat a broad range of chronic pain conditions. In addition, Z160 was well tolerated in previously conducted clinical trials involving over 200 subjects. Zalicus is advancing Z160 into Phase 2 clinical development for chronic neuropathic pain associated with Lumbosacral Radiculopathy (LSR) and post-herpetic neuralgia (PHN). LSR is a common neuropathic pain condition resulting from the compression or irritation of the nerve roots exiting the lumbar region of the spine. PHN is a painful neuropathic condition resulting from an outbreak of the herpes zoster virus, otherwise known as shingles.

N-type calcium channels have been recognized as key targets in controlling pain because of their key role in transmitting pain through the spinal nerves to the brain. Zalicus has utilized its expertise in this field to successfully discover high affinity, selective and orally available compounds, such as Z160, that show promise for further development as therapies for pain.

N-type Calcium Channel Blockers

N-type, or neural-type, calcium channel blockers represent a new class of analgesics that are selective for pain signal transmission. The concentration of calcium entering certain nerve cells in the spinal cord is directly linked to pain signal transmission. This pathway has been targeted by commercialized products such as Prialt^® and morphine-related drugs, both of which have been successful in treating severe and chronic pain but also have highly prohibitive routes of administration or side effects:

• Prialt is a peptide that must be delivered through a surgically implanted intrathecal pump (injected directly into the spinal cord), whereas Zalicus' N-type calcium channel blockers such as Z160 are being developed in oral form.
• Morphine and other related drugs affect N-type calcium channels indirectly by binding to opioid receptors. When morphine activates these receptors, it not only inhibits N-type calcium channels to affect pain signaling, but also affects other processes, which leads to side effects such as sedation, motor impairment, addiction and gastrointestinal problems. N-type specific calcium channel blockers are believed to avoid these serious side effects