Buprenorphine’s pharmacological and safety profile makes it an attractive treatment for patients addicted to opioids as well as for the medical professionals treating them. Buprenorphine is a partial agonist at the mu opioid receptor and an antagonist at the kappa receptor. It has very high affinity and low intrinsic activity at the mu receptor and will displace morphine, methadone, and other opioid full agonists from the receptor. Its partial agonist effects imbue buprenorphine with several clinically desirable pharmacological properties: lower abuse potential, lower level of physical dependence (less withdrawal discomfort), a ceiling effect at higher doses, and greater safety in overdose compared with opioid full agonists.
At analgesic doses, buprenorphine is 20-50 times more potent than morphine. Because of its low intrinsic activity at the mu receptor, however, at increasing doses, unlike a full opioid agonist, the agonist effects of buprenorphine reach a maximum and do not continue to increase linearly with increasing doses of the drug-the ceiling effect. One consequence of the ceiling effect is that an overdose of buprenorphine is less likely to cause fatal respiratory depression than is an overdose of a full mu opioid agonist.
In the pharmacotherapy of opioid addiction, buprenorphine, as a partial opioid agonist, can be thought of as occupying a midpoint between opioid full agonists (e.g., methadone, LAAM) and opioid antagonists (e.g., naltrexone, nalmefene). It has sufficient agonist properties such that individuals addicted to opioids perceive a reinforcing subjective effect from the medication, often described in terms of “feeling normal.”
In higher doses, and under certain circumstances, its antagonist properties can cause the precipitation of acute withdrawal if administered to an individual who is physically dependent on opioids and maintained on a sufficient dose of a full agonist. In this scenario, buprenorphine can displace the full agonist from the mu receptors, yet not provide the equivalent degree of receptor activation, thereby leading to a net decrease in agonist effect and the onset of withdrawal. Furthermore, because of the high affinity of buprenorphine for the opioid receptor, this precipitated abstinence syndrome may be difficult to reverse. Buprenorphine produces a blockade to subsequently administered opioid agonists in a dose-responsive manner. This effect makes the drug particularly appealing to well-motivated patients, as it provides an additional disincentive to continued opioid use.
Buprenorphine can produce euphoria, especially if it is injected. Buprenorphine does produce physical dependence, although it appears to do so to a lesser degree than do full opioid agonists, and it appears to be easier to discontinue at the end of medication treatment.
Buprenorphine has several pharmaceutical uses. It is a potent analgesic, available in many countries as a 0.3-0.4mg sublingual tablet (Temgesic). Until 2002, the only form of buprenorphine approved and marketed in the United States was the parenteral form for treatment of pain (Buprenex).