Apomorphine potency

When tested on prolactin release in isolated mammatrophs of bovine anterior pituitary, apomorphine appeared a full agonist (inhibiting release) while antagonism of the inhibition of prolactin release by the neuroleptics showed a potency more similar to that for binding than for blocking cAMP production. Also the inhibition of prolactin... 

In either the presence or absence of GTP, half-maximal stimulation of enzyme activity is achieved with 3 uM dopamine. Both 6,7-ADTM and epinine (K-methyl dopamine) stimulate adenylate cyclase activity to the same degree as does dopamine (Figure 8). In contrast, apomorphine is a partial agonist eliciting only 30 of the maximal effect of dopamine. The dopamine-stimulated adenylate cyclase activity is selectively blocked by cis-flupenthixol rather than the trans-isomer of this antagonist (JJL). Among the antagonists tested, the order of potency is cis-flupenthixol = fluphenazine > chlorpromazine > haloperidol > trans-flupenthixol (Table I). 

In fact the most important point concerns the very poor pharmacological characterization of the cAMP formation enhanced by dopamine and of the parathormone secretion. Firstly, apomorphine is much less potent than dopamine, a fact which is not compatible with what we know from pharmacological, behavioural and even biochemical studies (3,4 7) It is believed that apomorphine is a partial antagonist, but this has never been found in in vivo conditions. The higher potency of apomorphine is also reflected by its high affinity in %-haloperidol and 3H-spiperone binding. 

Figure 10. Comparison of the potency of apomorphine as a dopaminergic agonist upon intact 1L cells or cell-free homogenate of 1L tissue.

In the present study, R-(-)-apomorphine and three of its analogues were studied for their potency in decreasing the release of dopamine in the striatum after subcutaneous administration and for their oral bioavailability using the microdialysis technique in freely moving rats. 

The dose-response relationships of the test compounds are given in Figure 5.2. The response of the compounds is given as the AUC. To compare the AUCs, the experiments were stopped after 180 min. The rank order in the potency upon s.c. administration of the compounds is R-(-)-N-//-propylnorapomorphine (80) > R-(-)- l 1 -hydroxy-N-//-propylnoraporphine (12) > R-(-)-apomorphine (11). 

In conclusion, this microdialysis study shows that R-(-)-N- -propylnorapomorphine (80) and R-(-)-11 -hydroxy-N-//-propylnoraporphi ne (12) are more potent than R-(-)-apomorphine (11) in inhibiting dopamine release in the striatum. This difference in potency on the presynaptic receptors resembles the difference in potency of these analogues on supersensitive postsynaptic receptors as described by Kelly et al.269... 

We have shown, for instance, together with Aguettant, that, in solution, heparin, morphine, and apomorphine were almost totally destroyed by irradiation but that, if they were irradiated in the frozen state, at a low enough temperature, 100% of the activity/potency could be preserved. Nevertheless, at these low temperatures, in the frozen state, they became totally sterile under irradiation even after a massive initial contamination with Bacillus pumillus. 

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