Involvement of both dopaminergic and alpha-adrenergic receptors in the hypomotility induced by dibenzoyl-6,7-ADTN.
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 mumol/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 mumol/kg, i.p.), but haloperidol (0.3 mumol/kg, i.p.) and cis-flupenthixol (0.45 mumol/kg, i.p.) were without effect. The hypomotility due to DB-6,7-ADTN was also antagonised by yohimbine (13 mumol/kg, i.p.) and piperoxane (21 mumol/kg i.p.), drugs which act mainly by blocking presynaptic (alpha 2) adrenergic receptors. Prazosin (1.5 mumol/kg, i.p.), drugs which act mainly by blocking presynaptic (alpha 2) adrenergic receptors. Prazosin (1.5 mumol/kg, i.p.), a postsynaptic (alpha 1) adrenergic blocker, did not affect the hypomotility, and nor did a range of other neurotransmitter antagonists. DB-6,7-ADTN (50 mumol/kg, i.p.) was also found to antagonise the alpha-methyltyrosine (alpha-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.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003864:Depression, Chemical; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D009281:Naphthalenes; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D015016:Yohimbine; C026069:dibenzoyl 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene; D013469:Sulpiride; D003000:Clonidine