<unk>  comparison Drug RelativePotency NonionizedFraction ProteinBinding LipidSolubility Morphine 1 ++ ++ ++ Pethidine (meperidine) 0.1 + +++ +++ Hydromorphone 10 Alfentanil 10–25 ++++ ++++ +++ Fentanyl 75–125 + +++ ++++ Remifentanil 250 +++ +++ ++ Sufentanil 500–1000 ++ ++++ ++++ Etorphine 1000–3000 Carfentanil 10000<unk> s bind to specific<unk>  receptors in the nervous system and other tissues. There are three principal classes of<unk>  receptors, μ, κ, δ (mu, kappa, and delta), although up to seventeen have been reported, and include the ε, ι, λ, and ζ (Epsilon, Iota, Lambda and Zeta) receptors. Conversely, σ (Sigma) receptors are no longer considered to be<unk>  receptors because their activation is not reversed by the<unk>  inverse-agonist naloxone, they do not exhibit high-affinity binding for classical<unk> s, and they are stereoselective for dextro-rotatory isomers while the other<unk>  receptors are stereo-selective for levo-rotatory isomers. In addition, there are three subtypes of μ-receptor: μ1 and μ2, and the newly discovered μ3. Another receptor of clinical importance is the<unk> -receptor-like receptor 1 (ORL1), which is involved in pain responses as well as having a major role in the development of tolerance to μ-opioid agonists used as analgesics. These are all G-protein coupled receptors acting on GABAergic neurotransmission. Locants of the morphine molecule The pharmacodynamic response to an<unk>  depends upon the receptor to which it binds, its affinity for that receptor, and whether the<unk>  is an agonist or an antagonist. For example, the supraspinal analgesic properties of the<unk>  agonist morphine are mediated by activation of the μ1 receptor; respiratory depression and physical dependence by the μ2 receptor; and sedation and spinal analgesia by the κ receptor. Each group of<unk>  receptors elicits a distinct set of neurological responses, with the receptor subtypes (such as μ1 and μ2 for example) providing even more measurably specific responses. Unique to each<unk>  is its distinct binding affinity to the various classes of<unk>  receptors (e.g. the μ, κ, and δ<unk>  receptors are activated at different magnitudes according to the specific receptor binding affinities of the<unk> . For example, the opiate alkaloid morphine exhibits high-affinity binding to the μ-opioid receptor, while ketazocine exhibits high affinity to ĸ receptors. It is this combinatorial mechanism that allows for such a wide class of<unk> s and molecular designs to exist, each with its own unique effect profile. Their individual molecular structure is also responsible for their different duration of action, whereby metabolic breakdown (such as N-dealkylation) is responsible for<unk>  metabolism. INTA: selective agonist of KOR-DOR and KOR-MOR heteromers. Does not recruit β-arrestin II. Antinociceptive devoid of aversion, tolerance, and dependence in mice. Functional selectivity A new strategy of drug development takes receptor signal transduction into consideration. This strategy strives to increase the activation of desirable signalling pathways while reducing the impact on undesirable pathways. This differential strategy has been given several names, including functional selectivity and biased agonism. The first<unk>  that was intentionally designed as a biased agonist and placed into clinical evaluation is the drug oliceridine. It displays analgesic activity and reduced adverse effects.<unk>  comparison Extensive research has been conducted to determine equivalence ratios comparing the relative potency of<unk> s. Given a dose of an<unk> , an equianalgesic table is used to find the equivalent dosage of another. Such tables are used in<unk>  rotation practices, and to describe an<unk>  by comparison to morphine, the reference<unk> . Equianalgesic tables typically list drug half-lives, and sometimes equianalgesic doses of the same drug by means of administration, such as morphine: oral and intravenous. Binding profiles + Compound ' ' ' Ref 7-Hydroxymitragynine 13.5 155 123 β-Chlornaltrexamine 0.90 115 0.083 β-Endorphin 1.0 1.0 52 β-Funaltrexamine 0.33 48 2.8 Alazocine 2.7 4.1 3.2 (−)-Alazocine 3.0 15 4.7 (+)-Alazocine 1,900 19,000 1,600 Alfentanil 39 21,200 Binaltorphimine 1.3 5.8 0.79 18 0.66 55 Bremazocine 0.75 2.3 0.089 (−)-Bremazocine 0.62 0.78 0.075 Buprenorphine 4.18 25.8 12.9 Butorphanol 1.7 13 7.4 BW-3734 26 0.013 17 Carfentanil 0.024 3.3 43 Codeine 79 >1,000 >1,000 CTOP 0.18 >1,000 >1,000 Cyclazocine 0.45 6.3 5.9 Cyprodime 9.4 356 176 DADLE 16 0.74 >1,000 DAMGO 2.0 >1,000 >1,000 (D--AlaDeltorphin II >1,000 3.3 >1,000 Dermorphin 0.33 >1,000 >1,000 (+)-Desmetramadol 17 690 1,800 Dextropropoxyphene 34.5 380 1,220 Dezocine 3.6 290 460 Dihydroetorphine 0.45 1.82 0.57 Diprenorphine 0.072 0.23 0.017 DPDPE >1,000 14 >1,000 DSLET 39 4.8 >1,000 Dynorphin A 32 >1,000 0.5 Ethylketazocine 3.1 101 0.40 (−)-Ethylketazocine 2.3 5.2 2.2 (+)-Ethylketazocine 2,500 >10,000 1,600 Etorphine 0.23 1.4 0.13 Fentanyl 0.39 >1,000 255 Hydrocodone 11.1 962 501 Hydromorphone 0.47 18.5 24.9 ICI-204488 >1,000 >1,000 0.71 Leu-enkephalin 3.4 4.0 >1,000 Levacetylmethadol 9.86 169 1,020 Lofentanil 0.68 5.5 5.9 Met-enkephalin 0.65 1.7 >1,000 Metazocine 3.8 44.3 13.3 Methadone 1.7 435 405 Dextromethadone 19.7 960 1,370 Levomethadone 0.945 371 1,860 Methallorphan Dextrallorphan 1,140 2,660 34.6 Levallorphan 0.213 2.18 1,100 Methorphan Dextromethorphan 1,280 11,500 7,000 Levomethorphan 11.2 249 225 Mitragynine 7.24 60.3 1,100 Mitragynine pseudoindoxyl 0.087 3.02 79.4 Morphanol Dextrorphan 420 Levorphanol 0.42 3.61 4.2 Morphiceptin 56 >1,000 >1,000 Morphine 1.8 90 317 Morphine, (−)- 1.24 145 23.4 Morphine, (+)- >10,000 >100,000 >300,000 MR-2266 1.0 3.0 0.16 Nalbuphine 11 >1,000 3.9 Nalmefene 0.24 16 0.083 Nalorphine 0.97 148 1.1 Naloxonazine 0.054 8.6 11 Naloxone 1.1 16 12 (−)-Naloxone 0.93 17 2.3 (+)-Naloxone >1,000 >1,000 >1,000 Naltrexone 1.0 149 3.9 Naltriben 12 0.013 13 Naltrindole 64 0.02 66 Norbinaltorphimine 2.2 65 0.027 Normorphine 4.0 310 149 Ohmefentanyl 0.0079 10 32 Oxycodone 8.69 901 1,350 Oxymorphindole 111 0.7 228 Oxymorphone 0.78 50 137 Pentazocine 5.7 31 7.2 Pethidine (meperidine) 385 5,140 Phenazocine 0.20 5.0 2.0 PLO17 30 >1,000 >1,000 Quadazocine 0.99 2.6 0.5 Salvinorin A >10,000 >10,000 16 Samidorphan 0.052 2.6 0.23 33 1.7 >1,000 Spiradoline 21 >1,000 0.036 Sufentanil 0.15 50 75 Tianeptine 383 >10,000 >10,000 Tifluadom 32 189 2.1 Tramadol (+)-Tramadol (−)-Tramadol U-50488 >1,000 >1,000 0.12 U-69593 >1,000 >1,000 0.59 Xorphanol 0.25 1.0 0.4 Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. Assays were done mostly with cloned or cultured rodent receptors.
Opioid
Heroin
Synthetic cannabinoids
Nicotine
Phencyclidine
Cocaine 
Cocaine
Benzphetamine