Full antagonists

The approval of buprenorphine for the office-based treatment of opioid dependence represents a major departure from the earlier methadone clinic system. Physicians with addiction specialist credentials or those who have completed 8 hours of approved training can become qualified to treat up to 30 patients in their private offices. Stable patients may be given prescriptions for up to a month of medication. The combination buprenorphine/naloxone tablet is expected to have minimal risk for diversion. When taken subhnguaUy, as prescribed, naloxone has minimal biologic activity and does not interfere with the buprenorphine dose. However, if an attempt is made to inject the drug, the addict will experience the full antagonist effect of the naloxone. 

Extrapyramidal side-effects generally appear with blockade of dopamine D2 receptors in excess of 80%, whereas clinical efficacy in treating psychosis is associated with 60-70% D2 receptor blockade [12]. Recently, a partial agonist for the D2 receptor known as aripiprazole has been developed, which results in approximately 70% antagonism/30% agonism at the D2 receptor. It is an effective antipsychotic, has low risk for extrapyramidal symptoms, and does not cause elevated levels of prolactin as do the full antagonists at D2 receptors. 

Pike ACW, Brzozowski AM, Hubbard RE et al. Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. EM BO J. 18, 4608-4618, 1999. 

Laird, J. M. A., Mason, G. S., Webb, J., Hill, R. G., Hargreaves, R. J. Effects of a partial agonist and a full antagonist acting at the glycine site of the NMDA receptor on inflammation-induced mechanical hyperalgesia in rats, Br. J. Pharmacol. 1996, 117, 1487-1492. 

Thus, SR 120819A is the first, selective Yl-receptor antagonist displaying significant oral efficacy. Moreover, the absence of agonist activity detected for SR 120819A in these in vivo models confirms the full antagonist profile of this compound at NPY Y1 receptors. 

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