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Dopamine agonist activity of 8-OH-DPAT.

We have investigated the effects of 8-OH-DPAT in the mouse isolated vas deferens preparation and found it to possess a biphasic (initial inhibition followed by potentiation) dose-response curve. The initial inhibitory phase of the dose-response curve was not antagonized by naltrexone (300 nM), idazoxan (300 nM) or propranolol (300 nM), indicating that neither opioid, alpha 2- nor beta-receptors were involved in the inhibition. (+/-)-Cyanopindolol (300 nM) was also devoid of any antagonist activity versus 8-OH-DPAT, showing that the effect of the compound is not due to 5-HT1A or 5-HT1B agonist activity. Domperidone (10 nM), fluphenthixol (30 nM) and sulpiride, three chemically dissimilar DA2 antagonists, all antagonized the effects of DPAT, indicating that the compound is acting as a dopamine agonist in this preparation. A comparison, in the same preparations, of the agonist effects of DPAT and apomorphine, showed that DPAT possesses ca 0.01 the potency of apomorphine. The dose-response curve produced by DPAT was much shallower than that produced by apomorphine, indicating that DPAT is only a partial agonist in this preparation. This was confirmed by subsequent experiments which showed that DPAT, at a concentration of 3 microM, which had no effect on dose-response curves to the opioid agonist normorphine, produced a ca 10-fold shift in the dose-response curve to dopamine.