Respiratory depression is a potentially lethal side effect of morphine and other opioid painkillers but this unwanted effect is mediated through a separate signalling pathway to the analgesic effect of opioids. So US researchers sought to find a molecule that was more selective.
Using computational modelling, they screened the structure of more than three million molecules. Optimising the primary candidate led them to PZM21, a molecule that is highly selective for the analgesic opioid pathway. In mice, PZM21 was as effective an analgesic as morphine but there was little or no observed respiratory depression or morphine-like reinforcing activity, the team reports in Nature (online, 17 August 2016)
The molecule represents both a useful tool for disentangling opioid signalling and a drug candidate without many of the side effects associated with opioids, the researchers say.
Ugonjwa wa kupumua ni athari ya upande ya uwezekano wa kifo ya morphine na dawa nyingine za maumivu ya opioid, lakini athari hii isiyo ya lazima ni kuingiliwa kupitia njia tofauti ya ishara kwa athari ya analgesic ya opioids. Kwa hiyo, watafiti wa Marekani walitafuta molekuli yenye uwezo zaidi wa kuchagua. Kwa kutumia mbinu za kompyuta, walichunguza muundo wa molekuli zaidi ya milioni tatu. "Kupunguza kwa kiwango cha ""kuchukua"" kwa PZM21 ni hatua muhimu katika mchakato wa uponyaji wa maumivu." "PZM21 ilikuwa na ufanisi kama analgesic kama morphine, lakini kulikuwa na kidogo au hakuna kuonekana kupumua depressive au morphine-kama kuimarisha shughuli, ""mchoro katika Nature, 17 Agosti 2016."