Analgesic - cizolirtine
Despite the number of analgesic medicines available, problems with side-effects remain, whether they are the gastrointestinal difficulties associated with the standard non-steroidal anti-inflammatory drugs, or the systemic effects seen with opiates.
Despite the number of analgesic medicines available, problems with side-effects remain, whether they are the gastrointestinal difficulties associated with the standard non-steroidal anti-inflammatory drugs, or the systemic effects seen with opiates.
Another idea being explored for pain relief is stimulating the α2 adrenoceptors. These are believed to be involved in the sensory nociceptive processes of the spinal cord, and activating the noradrenergic pathways from the brain nuclei to the spinal cord. Selective α2 agonists have been shown to have analgesic effects in rats. In addition, the α2 adrenoceptors are believed to be involved in the inhibition of substance P release by noradrenaline. Substance P is also implicated in the transmission of nociceptive information.
Cizolirtine citrate is a potential new analgesic that acts by this mechanism, and is being investigated by Laboratorios Dr Esteve.1 Placebo-controlled clinical studies in more than 1000 subjects have now been carried out, with the drug being administered orally, intramuscularly or intravenously. Around a quarter of the subjects were healthy volunteers. Those given the drug orally received single escalating doses of 400, 600 and 800mg, and repeated oral dose tolerability studies of 300 and 400mg twice a day for two weeks, with no severe adverse events. Intramuscular doses of 20-300mg were similarly free from side-effects, as were 15-minute intravenous infusions of 26-400mg.
Several inflammatory pain studies have been carried out, including wisdom teeth extractions and migraines, though these were somewhat hampered by placebo effects. Similar placebo effects were also seen in neuropathic pain, but patients with primary allodynia saw a significant improvement with the active. Experimental pain studies, however, showed 100mg cizolirtine citrate to have similar activity to 100mg diclofenac. Two further Phase II studies using higher doses of the medicine, one in cancer pain and the other in renal colic, showed significant pain relief activity.2
Cizolirtine is well tolerated and at higher doses it clearly has potential as an analgesic for several indications, including neuropathic disorders.