Induction by Dopamine D1 Receptor Agonist ABT-431 of Dyskinesia Similar to Levodopa in Patients With Parkinson Disease

Abstract

Dopamine D(1) agonists can induce a full antiparkinsonian response but do not support previous hypotheses suggesting that D(1) agonists are more or less likely to produce dyskinesias than levodopa.

Abnormal involuntary movement (AIM) expression following D2 dopamine agonist challenge is determined by the nature of prior dopamine receptor stimulation (priming) in 6-hydroxydopamine lesioned rats

“…For the doses of dopamine agonists used, we found that D2-priming produced AIMs of lower overall intensity than those observed following priming with D1/D2 and D1 agonists in 6-OHDA rats. This finding is consistent with studies that measured the combined total AIMs in 6-OHDA rats (Carta et al, 2008a;Lundblad et al, 2002;Monville et al, 2005), and also with reports that D2 agonists produce lower intensity dyskinesias than L-dopa or D1 agonists in primate models of PD (Calon et al, 1999;Pearce et al, 1998;Smith et al, 2006) and human PD patients (Olanow, 2002;Rascol et al, 2000Rascol et al, , 2001Rascol et al, , 2006. Our data also showed that D2 priming produced AIMs of lesser complexity than priming with D1/D2 and D1 agonists in 6-OHDA rats.…”

Abnormal involuntary movement (AIM) expression following D2 dopamine agonist challenge is determined by the nature of prior dopamine receptor stimulation (priming) in 6-hydroxydopamine lesioned rats

“…For the doses of dopamine agonists used, we found that D2-priming produced AIMs of lower overall intensity than those observed following priming with D1/D2 and D1 agonists in 6-OHDA rats. This finding is consistent with studies that measured the combined total AIMs in 6-OHDA rats (Carta et al, 2008a;Lundblad et al, 2002;Monville et al, 2005), and also with reports that D2 agonists produce lower intensity dyskinesias than L-dopa or D1 agonists in primate models of PD (Calon et al, 1999;Pearce et al, 1998;Smith et al, 2006) and human PD patients (Olanow, 2002;Rascol et al, 2000Rascol et al, , 2001Rascol et al, , 2006. Our data also showed that D2 priming produced AIMs of lesser complexity than priming with D1/D2 and D1 agonists in 6-OHDA rats.…”

Striatal Signaling in L-DOPA-Induced Dyskinesia: Common Mechanisms with Drug Abuse and Long Term Memory Involving D1 Dopamine Receptor Stimulation

“…In summary, D1R stimulation seems to be necessary for LID development and sufficient to induce dyskinetic movements. This is in agreement with data showing that, in contrast to D2-like receptor agonists (most of which have a high affinity for the D3R – Rascol, 1999), D1-like receptor agonists are markedly dyskinetogenic in monkeys rendered parkinsonian by MPTP (Doucet et al, 1996) as well as in patients (Rascol et al, 2001). Additional mechanisms involving D2 family receptors may contribute to the expression of LID, especially when dyskinetic movements are induced by D2-like agonists in animals previously exposed to l -DOPA.…”

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

“…Our present findings confirm that D1/D5 agonists can induce AIMs in parkinsonian rodents (Monville et al, 2005). Studies performed in MPTP-lesioned monkeys are to some extent contradictory on this matter, yet most emphasize that D1/D5 agonists induce significant dyskinesia (Blanchet et al, 1996;Pearce et al, 1999;Goulet and Madras, 2000) and the D1/D5 agonist ABT-431 is as potent as levodopa in inducing dyskinesia in patients (Rascol et al, 2001). Remarkably, we found that SKF-81297 induced significantly more MD than apomorphine and quinpirole, what is consistent with reports showing that D1/D5 agonists increase oral movements in rats and monkeys with intact dopaminergic pathways (Bedard and Boucher, 1989;Waddington et al, 1995) and produce abnormal dyskinetic oral movements in MPTP-lesioned marmosets (Gnanalingham et al, 1995).…”

“…But the neural mechanisms of dopamine agonist-induced dyskinesia are thought to essentially concern the indirect pathway (Crossman, 1990;Obeso et al, 2000) and our findings suggest a primary involvement of the D1 receptor regulated direct pathway. A primary involvement of D1 receptors and the direct basal ganglia pathway is suggested by other recent studies too (Aubert et al, 2005;Fiorentini et al, 2006), and by the fact that D2 family agonists are less likely to induce dyskinesia in patients and animal models of PD than unselective and D1/D5 selective agonists (present findings; Gnanalingham et al, 1995;Blanchet et al, 1996;Pearce et al, 1999;Goulet and Madras, 2000;Nutt, 2000;Rascol et al, 2001;Lundblad et al, 2002;Monville et al, 2005). A recent study established that levodopa-induced dyskinesia in the rat 6-OHDA model is related to increased synchronization of afferent activity to the basal ganglia output nuclei (Meissner et al, 2006).…”

Abnormal involuntary movement (AIM) expression following D2 dopamine agonist challenge is determined by the nature of prior dopamine receptor stimulation (priming) in 6-hydroxydopamine lesioned rats

“…For the doses of dopamine agonists used, we found that D2-priming produced AIMs of lower overall intensity than those observed following priming with D1/D2 and D1 agonists in 6-OHDA rats. This finding is consistent with studies that measured the combined total AIMs in 6-OHDA rats (Carta et al, 2008a;Lundblad et al, 2002;Monville et al, 2005), and also with reports that D2 agonists produce lower intensity dyskinesias than L-dopa or D1 agonists in primate models of PD (Calon et al, 1999;Pearce et al, 1998;Smith et al, 2006) and human PD patients (Olanow, 2002;Rascol et al, 2000Rascol et al, , 2001Rascol et al, , 2006. Our data also showed that D2 priming produced AIMs of lesser complexity than priming with D1/D2 and D1 agonists in 6-OHDA rats.…”

Striatal Signaling in L-DOPA-Induced Dyskinesia: Common Mechanisms with Drug Abuse and Long Term Memory Involving D1 Dopamine Receptor Stimulation

“…In summary, D1R stimulation seems to be necessary for LID development and sufficient to induce dyskinetic movements. This is in agreement with data showing that, in contrast to D2-like receptor agonists (most of which have a high affinity for the D3R – Rascol, 1999), D1-like receptor agonists are markedly dyskinetogenic in monkeys rendered parkinsonian by MPTP (Doucet et al, 1996) as well as in patients (Rascol et al, 2001). Additional mechanisms involving D2 family receptors may contribute to the expression of LID, especially when dyskinetic movements are induced by D2-like agonists in animals previously exposed to l -DOPA.…”

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

“…Our present findings confirm that D1/D5 agonists can induce AIMs in parkinsonian rodents (Monville et al, 2005). Studies performed in MPTP-lesioned monkeys are to some extent contradictory on this matter, yet most emphasize that D1/D5 agonists induce significant dyskinesia (Blanchet et al, 1996;Pearce et al, 1999;Goulet and Madras, 2000) and the D1/D5 agonist ABT-431 is as potent as levodopa in inducing dyskinesia in patients (Rascol et al, 2001). Remarkably, we found that SKF-81297 induced significantly more MD than apomorphine and quinpirole, what is consistent with reports showing that D1/D5 agonists increase oral movements in rats and monkeys with intact dopaminergic pathways (Bedard and Boucher, 1989;Waddington et al, 1995) and produce abnormal dyskinetic oral movements in MPTP-lesioned marmosets (Gnanalingham et al, 1995).…”

“…But the neural mechanisms of dopamine agonist-induced dyskinesia are thought to essentially concern the indirect pathway (Crossman, 1990;Obeso et al, 2000) and our findings suggest a primary involvement of the D1 receptor regulated direct pathway. A primary involvement of D1 receptors and the direct basal ganglia pathway is suggested by other recent studies too (Aubert et al, 2005;Fiorentini et al, 2006), and by the fact that D2 family agonists are less likely to induce dyskinesia in patients and animal models of PD than unselective and D1/D5 selective agonists (present findings; Gnanalingham et al, 1995;Blanchet et al, 1996;Pearce et al, 1999;Goulet and Madras, 2000;Nutt, 2000;Rascol et al, 2001;Lundblad et al, 2002;Monville et al, 2005). A recent study established that levodopa-induced dyskinesia in the rat 6-OHDA model is related to increased synchronization of afferent activity to the basal ganglia output nuclei (Meissner et al, 2006).…”

Abnormal involuntary movement (AIM) expression following D2 dopamine agonist challenge is determined by the nature of prior dopamine receptor stimulation (priming) in 6-hydroxydopamine lesioned rats

“…For the doses of dopamine agonists used, we found that D2-priming produced AIMs of lower overall intensity than those observed following priming with D1/D2 and D1 agonists in 6-OHDA rats. This finding is consistent with studies that measured the combined total AIMs in 6-OHDA rats (Carta et al, 2008a;Lundblad et al, 2002;Monville et al, 2005), and also with reports that D2 agonists produce lower intensity dyskinesias than L-dopa or D1 agonists in primate models of PD (Calon et al, 1999;Pearce et al, 1998;Smith et al, 2006) and human PD patients (Olanow, 2002;Rascol et al, 2000Rascol et al, , 2001Rascol et al, , 2006. Our data also showed that D2 priming produced AIMs of lesser complexity than priming with D1/D2 and D1 agonists in 6-OHDA rats.…”

Striatal Signaling in L-DOPA-Induced Dyskinesia: Common Mechanisms with Drug Abuse and Long Term Memory Involving D1 Dopamine Receptor Stimulation

“…In summary, D1R stimulation seems to be necessary for LID development and sufficient to induce dyskinetic movements. This is in agreement with data showing that, in contrast to D2-like receptor agonists (most of which have a high affinity for the D3R – Rascol, 1999), D1-like receptor agonists are markedly dyskinetogenic in monkeys rendered parkinsonian by MPTP (Doucet et al, 1996) as well as in patients (Rascol et al, 2001). Additional mechanisms involving D2 family receptors may contribute to the expression of LID, especially when dyskinetic movements are induced by D2-like agonists in animals previously exposed to l -DOPA.…”

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

“…Our present findings confirm that D1/D5 agonists can induce AIMs in parkinsonian rodents (Monville et al, 2005). Studies performed in MPTP-lesioned monkeys are to some extent contradictory on this matter, yet most emphasize that D1/D5 agonists induce significant dyskinesia (Blanchet et al, 1996;Pearce et al, 1999;Goulet and Madras, 2000) and the D1/D5 agonist ABT-431 is as potent as levodopa in inducing dyskinesia in patients (Rascol et al, 2001). Remarkably, we found that SKF-81297 induced significantly more MD than apomorphine and quinpirole, what is consistent with reports showing that D1/D5 agonists increase oral movements in rats and monkeys with intact dopaminergic pathways (Bedard and Boucher, 1989;Waddington et al, 1995) and produce abnormal dyskinetic oral movements in MPTP-lesioned marmosets (Gnanalingham et al, 1995).…”

“…But the neural mechanisms of dopamine agonist-induced dyskinesia are thought to essentially concern the indirect pathway (Crossman, 1990;Obeso et al, 2000) and our findings suggest a primary involvement of the D1 receptor regulated direct pathway. A primary involvement of D1 receptors and the direct basal ganglia pathway is suggested by other recent studies too (Aubert et al, 2005;Fiorentini et al, 2006), and by the fact that D2 family agonists are less likely to induce dyskinesia in patients and animal models of PD than unselective and D1/D5 selective agonists (present findings; Gnanalingham et al, 1995;Blanchet et al, 1996;Pearce et al, 1999;Goulet and Madras, 2000;Nutt, 2000;Rascol et al, 2001;Lundblad et al, 2002;Monville et al, 2005). A recent study established that levodopa-induced dyskinesia in the rat 6-OHDA model is related to increased synchronization of afferent activity to the basal ganglia output nuclei (Meissner et al, 2006).…”