Involvement of both dopaminergic and α-adrenergic receptors in the hypomotility induced by dibenzoyl-6,7-ADTN

Abstract

The dopaminergic prodrug dibenzoyl-6,7-ADTN (DB-6,7-ADTN) can enter the brain following intraperitoneal injection and be hydrolysed to produce low concentrations of the dopamine agonist 6,7-ADTN. Intraperitoneal injections of DB-6,7-ADTN produce a decrease in motor activity and in the present study this response has been characterised, and the underlying mechanisms examined. Doses of 10–100 μmol/kg DB-6,7-ADTN elicit a strong hypomotive response, which is dose dependent. Treated animals are significantly less active than controls. DB-6,7-ADTN hypomotility was significantly attenuated by the non-sedative dopamine receptor antagonist sulpiride (62 μmol/kg, i.p.), but haloperidol (0.3 μmol/kg, i.p.) and cis-flupenthixol (0.45 μmol/kg, i.p.) were without effect. The hypomotility due to DB-6,7-ADTN was also antagonised by yohimbine (13 μmol/kg, i.p.) and piperoxane (21 μmol/kg i.p.), drugs which act mainly by blocking presynaptic ( α 2) adrenergic receptors. Prazosin (1.5 μmol/ kg, i.p.), a postsynaptic ( α 1) adrenergic blocker, did not affect the hypomotility, and nor did a range of other neurotransmitter antagonists. DB-6,7-ADTN (50 μmol/kg, i.p.) was also found to antagonise the α-methyltyrosine (α-MT, 1.02 mmol/kg, i.p.) induced fall in noradrenaline and dopamine levels in brain and spinal cord. Inhibition of the effects of DB-6,7-ADTN on noradrenaline and dopamine turnover by yohimbine and sulpiride, respectively, suggests that 6,7-ADTN (derived from the prodrug) has alpha adrenergic as well as dopaminergic activity. The results are discussed in connection with the hypomotive effects of other dopamine agonists.