Abstract
The effects of co-administration of quinpirole with benzazepine D1 dopamine (DA) agonists possessing full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393 and SKF 75670) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) were investigated in rodent and primate models of Parkinson's disease (PD). In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, co-administration of SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine), SKF 75670 (3-CH3 analogue), SKF 80723 (6-Br analogue), SKF 83959 (6-Cl, 3-CH3, 3′-CH3 analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) strongly potentiated the contralateral circling induced by quinpirole. In MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated common marmosets, administration of quinpirole alone increased locomotor activity and reversed motor deficits. Grooming and oral activity were unaltered. Co-administration of SKF 38393 and SKF 75670 inhibited the quinpirole-induced changes in locomotor activity and motor disability. The combined treatment of SKF 80723 or SKF 82958 with quinpirole had no overall effect on locomotor activity or motor disability. In contrast, SKF 83959 extended the duration of the quinpirole-induced increase in locomotor activity with corresponding decreases in motor disability. Co-administration of high doses of SKF 82958 and more especially SKF 83959 and SKF 80723, with quinpirole induced hyperexcitability and seizures. Oral activity and grooming were unaltered following the co-administration of benzazepine derivatives with quinpirole. The ability of some benzazepine D1 DA agonists to prolong the antiparkinsonian effects of quinpirole in the MPTP-treated marmoset may indicate a role for certain D1 DA agonists in the clinical treatment of PD. In general, the behavioural responses to the combined administration of benzazepines with quinpirole in the 6-OHDA lesioned rat and more especially the MPTP-treated marmoset failed to correlate with their ability to stimulate AC. These observations further implicate a behavioural role for D1 DA receptors not linked to AC.
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Arnt J (1985a) Behavioural stimulation is induced by separate dopamine D1 and D2 receptors in reserpine-pretreated but not in normal rats. Eur J Pharmacol 113:79–88
Arnt J (1985b) Hyperactivity induced by stimulation of separate dopamine D1 and D2 receptors in rats with bilateral 6-OHDA lesions. Life Sci 37:717–723
Arnt J, Hyttel J (1984) Differential inhibition by dopamine D1 and D2 antagonists of circling behaviour induced by dopamine agonists in rats with unilateral 6-hydroxydopamine lesions. Eur J Pharmacol 102:349–354
Arnt J, Bogeso KP, Hyttel J, Meier E (1988) Relative dopamine D1 and D2 receptor affinity and efficacy determine whether dopamine agonists induce hyperactivity or oral stereotypy in rats. Pharmacol Toxicol 62:121–130
Arnt J, Hyttel J, Sanchez C (1992) Partial and full dopamine D1 receptor agonists in mice and rats: relation between behavioural effects and stimulation of adenylate cyclase activity in vitro. Eur J Pharmacol 213:259–267
Barone P, Davis TA, Braun AR, Chase TN (1986) Dopaminergic mechanisms and motor function: characterisation of D1 and D2 dopamine receptor interactions. Eur J Pharmacol 123:109–114
Battaglia G, Norman AB, Hess EJ, Creese I (1986) Functional recovery of D1 dopamine receptor mediated stimulation of rat striatal adenylate cyclase activity following irreversible modification byN-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ): evidence for spare receptors. Neurosci Lett 69:290–295
Bedard PJ, Boucher R (1989) Effect of D1 receptor stimulation in normal and MPTP monkeys. Neurosci Lett 104:223–228
Bertorello AM, Hopfield JF, Aperia A, Greengard P (1990) Inhibition by dopamine of (Na+/K+) ATPase activity in neostriatal neurones through D1 and D2 dopamine receptor synergism. Nature 347:386–388
Boyce S, Rupniak NMJ, Steventon MJ, Iversen SD (1990) Differential effects of D1 and D2 agonists in MPTP-treated primates: functional implications for Parkinson's disease. Neurology 40:927–933
Braun A, Fabbrini G, Mouradian MM, Serrati C, Barone P, Chase TN (1987) Selective D1 dopamine agonist treatment of Parkinson's disease. J Neural Transm 68:41–50
Close SP, Marriott AS, Pay S (1985) Failure of SKF 38393-A to relieve parkinsonian symptoms induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset. Br J Pharmacol 85:320–322
Close SP, Elliott PJ, Hayes AG, Marriott AS (1990) Effects of classical and novel agents in a MPTP-induced reversible model of Parkinson's disease. Psychopharmacology 102:295–300
Collins P, Broekkamp CLE, Jenner P, Marsden CD (1991) Drugs acting at D1 and D2 dopamine receptors induce identical purposeless chewing in rats which can be differentiated by cholinergic manipulation. Psychopharmacology 103:503–512
Dall'Olio R, Gandolfi O, Vaccheri A, Roncada P, Montanaro N (1988) Changes in behavioural responses to the combined administration of D1 and D2 dopamine agonists in normosensitive and D1 supersensitive rats. Psychopharmacology 95:381–385
Daly SA, Waddington JL (1992) D1 dopamine receptors and the topography of unconditioned motor behaviour: studies with the selective, “full efficacy” benzazepine D1 agonist SKF 83189. J Psychopharmacol 6:50–60
DeNinno MP, Schoenleber R, MacKenzie R, Britton DR, Asin KE, Briggs C, Trugman JM, Ackerman M, Artman L, Bednarz L, Bhatt R, Curzon P, Gomez E, Kang CH, Stitts J, Kebabian JW (1991) A68930: a potent agonist selective for the dopamine D1 receptor. Eur J Pharmacol 199:209–219
Domino EF, Sheng J (1993) Relative potency and efficacy of some dopamine agonists with varying selectivities for D1 and D2 receptors in MPTP-induced hemiparkinsonian monkeys. J Pharmacol Exp Ther 265:1387–1391
Downes RP, Waddington JL (1993) Grooming and vacuous chewing induced by SKF 83959 and agonist of dopamine “D1 like” receptors that inhibits dopamine sensitive adenylyl cyclase. Eur J Pharmacol 234:135–136
Emre M, Rinne UK, Rascol A, Lees A, Agid Y, Lataste X (1992) Effects of a selective partial D1 agonist, CY 208–243, in de novo patients with Parkinson's disease. Mov Disord 7:239–243
Gnanalingham KK, Erol DD, Hunter AJ, Smith LA, Jenner P, Marsden CD (1994) The differential antiparkinsonian effects of benzazepine D1 dopamine agonists with varying efficacies in the MPTP-treated marmoset. Psychopharmacology
Gower AJ, Marriott A (1982) Pharmacological evidence for the subclassification of central dopamine receptors in the rat. Br J Pharmacol 77:185–194
Hess EJ, Battaglia G, Norman AB, Creese (1987) Differential modification of striatal D1 dopamine receptors and effector moieties byN-ethoxycarbonyl-2-thoxy-1,2-dihydroquinoline in vivo and in vitro. J Pharmacol Exp Ther 31:50–57
Itoh Y, Beaulieu M, Kebabian J (1984) The chemical basis for the blockade of the D1 dopamine receptor by SCH 23390. Eur J Pharmacol 100:119–122
Izenwasser S, Katz J (1993) Differential efficacies of dopamine D1 receptor agonists for stimulating adenylyl cyclase in squirrel monkey and rat. Eur J Pharmacol - [Mol Pharmacol] 246:39–44
Johansen PA, Hu X-T, White FJ (1991) Relationship between D1 dopamine receptors, adenylate cyclase and the electrophysiological responses of rat nucleus accumbens neurones. J Neural Transm 86:97–113
Johansson P, Levin E, Gunne L, Ellison G (1987) Opposite effects of D1 and D2 agonist on oral movements in rats. Eur J Pharmacol 134:83–88
Kebabian JW, Britton DR, DeNinno MP, Perner R, Smith L, Jenner P, Schoenleber R, Williams M (1992) A77636: A potent and selective dopamine D1 receptor agonist with antiparkinsonian activity in marmosets. Eur J Pharmacol 229:203–209
Loschmann PA, Smith LA, Lange KW, Jaehnig P, Jenner P, Marsden CD (1991) Motor activity following the administration of selective D1 and D2 dopaminergic drugs to normal common marmosets. Psychopharmacology 105:303–309
Loschmann PA, Smith LA, Lange KW, Jaehnig P, Jenner P, Marsden CD (1992) Motor activity following the administration of selective D1 and D2 dopaminergic drugs to MPTP-treated common marmosets. Psychopharmacology 109:49–56
Lovenberg TW, Brewster WK, Mottola DM, Lee RC, Riggs RM, Nichols DE, Lewis MH, Mailman RB (1989) Dihydrexidine, a novel selective high potency full dopamine D1 receptor agonist. Eur J Pharmacol 166:111–113
Madras BK, Fahey MA, Canfield DR, Spealman RD (1988) D1 and D2 dopamine receptors in caudate-putamen of non-human primates (Macaca fascicularis). J Neurochem 51:934–943
Mahan LC, Burch RM, Monsma FJ, Sibley DR (1990) Expression of striatal D1 dopamine receptors coupled to inositol phosphate production and Ca2+ mobilisation inXenopus oocytes. Proc Natl Acad Sci 87:2196–2200
Mailman RB, Schulz DW, Kilts CD, Lewis MH, Rollema H, Wyrick S (1986) The multiplicity of the D1 dopamine receptor. Neurobiology of central D1 dopamine receptors. In: Breese GR, Creese I (eds) Adv Exp Med Biol 204:53–72
Markstein R, Seiler NP, Vigouret JM, Urwyler S, Enz A, Dixon K (1988) Pharmacological properties of CY 208–243, and normal D1 agonists, In Sandler M. ed. Proceedings of XIth international catecholamine symposium Part B: Central aspects. Alan R Liss, New York, pp 59–64
Mashurano M, Waddington JL (1986) Stereotyped behaviour in response to the selective D2 dopamine agonist RU 24213 is enhanced by pretreatment with the selective D1 agonist SK&F 38393. Neuropharmacology 25:947–949
Murray AM, Waddington JL (1989) The induction of grooming and vacuous chewing by a series of selective D1 dopamine agonists: two directions of D1:D2 interaction. Eur J Pharmacol 160: 377–384
Nomoto M, Jenner P, Marsden CD (1985) The dopamine D2 agonist LY 141865, but not the D1 agonist SKF 38393 reverses parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset. Neurosci Lett 57:37–41
Nomoto M, Jenner P, Marsden CD (1988) The D1 agonist SKF 38393 inhibits the antiparkinsonian activity of the D2 agonist LY 171555 in the MPTP-treated marmoset. Neurosci Lett 93:275–280
O'Boyle KM, Waddington JL (1987) [3H]-SCH 23390 binding to human putamen D1 dopamine receptors: stereochemical and structure-affinity relationships among 1-phenyl-1H-3-benzazepine derivatives as a guide to D1 receptor topography. J Neurochem 48:1039–1042
O'Boyle KM, Gaitanopoulos DE, Brenner M, Waddington JL (1989) Agonist and antagonist properties of benzazepine and thienopyridine derivatives at the D1 dopamine receptor. Neuropharmacology 28:401–405
Peacock L, Lublin H, Gerlach J (1990) The effects of dopamine D1 and D2 receptor agonists and antagonists in monkeys withdrawn from long-term neuroleptic treatment. Eur J Pharmacol 186:49–59
Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Plenum Press, London
Pifl C, Reither H, Hornykiewicz O (1991) Lower efficacy of the dopamine D1 agonist, SKF 38393, to stimulate adenylyl cyclase activity in primate than in rodent striatum. Eur J Pharmacol 202:273–276
Piomelli D, Pilon C, Giros B, Sokoloff P, Martes M-P, Schwartz J-C (1991) Dopamine activation of the arachidonic acid cascade as a basis for D1/D2 receptor synergism. Nature 353:164–167
Robertson GS, Robertson HA (1986) Synergistic effects of D1 and D2 dopamine agonists on turning behaviour in rats. Brain Res 384:387–390
Rosengarten H, Schweitzer JW, Friedhoff AJ (1986) Selective dopamine D2 receptor reduction enhances a D1 mediated oral dyskinesia in rats. Life Sci 39:29–35
Rouillard C, Bedard PJ (1988) Specific D1 and D2 dopamine agonists have synergistic effects in the 6-hydroxydopamine circling model in the rat. Neuropharmacology 27:1257–1264
Rouillard C, Bedard PJ, Di Paolo T (1990) Effects of chronic treatment of MPTP monkeys with bromocriptine alone or in combination with SKF 38393. Eur J Pharmacol 185:209–215
Rupniak NMJ, Boyce S, Steventon M, Iversen SD (1992) Weak antiparkinsonian activity of the D1 agonist C-APB (SKF 82958) and lack of synergism with a D2 agonist in primates. Clin Neuropharmacol 15:307–309
Schoors DF, Vauquelin GP, Vos HD, Smets G, Velkeniers B, Vanhaelst L, Dupont AG (1991) Identification of a D1 dopamine receptor, not linked to adenylate cyclase, on lactotroph cells. Br J Pharmacol 103:1928–1934
Setler PE, Sarau HM, Zirkle CL, Saunders HL (1978) The central effects of a novel dopamine agonist. Eur J Pharmacol 50:419–430
Sibley DR, Monsma FJ (1992) Molecular biology of dopamine receptors. Trends Pharmacol Sci 13:61–69
Sokoloff P, Giros B, Martres M-P, Bouthenet M-L, Schwartz J-C (1990) Molecular cloning and characterisation of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 34:146–151
Sunahara RK, Guan H-C, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HHM, Niznik HB (1991) Cloning of the gene for a human dopamine D5 receptor with high affinity for dopamine than D1. Nature 350:614–619
Undie AS, Friedman E (1990) Stimulation of a dopamine D1 receptor enhances inositol phosphates formation in rat brain. J Pharmacol Exp Ther 253:987–992
Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal system. Brain Res 14:461–471.
Watts VJ, Lawler CP, Gilmore JH, Southerland SB, Nichols DE, Mailman RB (1993) Dopamine D1 receptors: efficacy of full (dihydrexidine) vs. partial (SKF 38393) agonists in primates vs. rodents. Eur J Pharmacol 24:165–172
Weinstock J, Hieble JP, Wilson JW (1985) The chemistry and pharmacology of 3-benzazepine derivatives. Drugs Future 10:645–696
Weinstock J, Ladd DL, Wilson JW, Brush CK, Yim NCF, Gallagher G, McCarthy ME, Silvestri J, Sarau HM, Flaim KE, Ackerman DM, Setler PE, Tobia AJ, Hahn RA (1986) Synthesis and renal vasodilator activity of some dopamine agonist 1-aryl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diols: halogen and methyl analogues of fenoldopam. J Med Chem 29:2315–2325
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Gnanalingham, K.K., Jenner, P., Hunter, A.J. et al. The differential behavioural effects of benzazepine D1 dopamine agonists with varying efficacies, co-administered with quinpirole in primate and rodent models of Parkinson's disease. Psychopharmacology 117, 287–297 (1995). https://doi.org/10.1007/BF02246103
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DOI: https://doi.org/10.1007/BF02246103