Table 8.
Some Nonselective and Selective Oxytocin Antagonists in the Rat.
| Antioxytocic (anti-OT) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| In vitro pA2a | In vivo | Antivasopressor (anti-V1a) | Antidiuretic activity (V2) | ||||||
| Number | Peptide | No Mg2+ | EDa | pA2c | EDb | pA2c | Units/mg | ED ratiod | Ref |
| 1 | d[D-Tyr(Et)2,Thr4]OVT (atosiban) | 8.29 | Antagonist | Agonist 0.02 (IU/μmol) | Agonist 0.04 (IU/μmol) | 106 | |||
| 7.71 | 5.95 | 7.05 | 48.5 | 6.14 | Antagonist (pA2 ≍ 5.9) | 8 | 104 | ||
| 2 | d(CH2)5[Tyr(Me)2]OVT | 8.52 | 4.2 | 7.37 | 0.80 | 7.96 | ≍ 0.01 | 0.2 | 103 |
| 3 | desGly-NH2,d(CH2)5[Tyr(Me)2, Thr4]OVT | 7.89 | 1.3 | 7.69 | 23 | 6.48 | Antagonist (pA2 ≍ 5.5) | 17.7 | 104 |
| 4 | d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH29 ]OVT | 7.63 | 1.0 | 7.83 | 6.6 | 7.02 | ≍ 0.015 | 6.6 | 104, 105 |
| 5 | desGly-NH2,d(CH2)5[D-Tyr2, Thr4]OVT | 7.77 | 2.85 | 7.37 | 272 | 5.39 | Antagonist (pA2 < 5.5) | 95 | 104 |
a
In vitro pA2 values represents the negative logarithm to the base 10 of the average molar concentration [m] of antagonist which reduces the response to 2 × units of agonist to the response with × units of agonist. bThe effective dose (ED) is defined as the dose (in nm/kg) of antagonist that reduces the response to 2 × units of agonist to the response with × units of agonist administered in the absence of antagonist. cEstimated in vivo pA2 values represent the negative logarithms of the ‘effective dose’ divided by the estimated volume of distribution (67 ml/kg) (52). dED ratio = anti-vasopressor ED/antioxytocic ED.