D2 and D1 dopaminergic activity of 7-OH-DPAT.
The D1 and D2 dopamine receptor agonist properties of 7-hydroxy-2-(N,N-di-n-propylamino) tetraline (7-OH-DPAT) was determined by investigating the effect of this compound on rat striatal acetylcholine (ACh) concentration and increase in cAMP formation in primary cerebellar granule cell cultures. 7-OH-DPAT at low doses (0.01 to 0.1 mumol/ kg) had no significant effect, and at high doses (0.3 to 30 mumol/kg) significantly (P < 0.01) increased striatal ACh levels. Likewise, quinpirole was found to significantly elevate ACh content. Pretreatment with haloperidol, a non-selective antagonist of the D2 family of receptors, significantly (P < 0.01) blocked 7-OH-DPAT- and quinpirole-induced increases in ACh. U-99194A, a D3 selective dopamine antagonist, had no significant effect on 7-OH-DPAT-induced increases in striatal ACh. However, raclopride, a D2 selective dopamine antagonist, completely blocked 7-OH-DPAT-induced elevations in ACh. 7-OH-DPAT in the mumolar range increased cAMP formation in granule cell cultures, and this effect was antagonized by SCH 23390, a D1 selective dopamine antagonist. The neurochemical study indicates that, at high doses, 7-OH-DPAT has both D1 and D2 agonist activities.
Pharmacia & Upjohn Inc., Kalamazoo, MI 49001, USA.
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology; D000242:Cyclic AMP / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007189:Indans; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D006220:Haloperidol; D000109:Acetylcholine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin