The rationale for the use of dopamine agonists in parkinson's disease

Peter Jenner; J. C. Schwartz; N. Giros; M. P. Matres; D. R. Sibley; F. J. Monsma; P. Sokoloff; M. P. Martres; B. Giros; G. E. Martin; M. Williams; D. J. Pettibone; M. Nomoto; S. Stahl; P. Jenner; R. J. Coleman; K. W. Lange; N. P. Quinn; P. A. Loschmann; P. N. Chong; M. Nomoto; P. E. Setler; H. M. Sarau; C. L. Zirkle; M. Nomoto; P. Jenner; C. D. Marsden; P. Barone; K. S. Bankiewicz; G. U. Corsini; M. Nomoto; P. Jenner; C. D. Marsden; A. Braun; G. Fabbrini; M. M. Mouradian; J. A. Temlett; P. N. Chong; W. H. Oertel; J. A. Temlett; N. P. Quinn; P. G. Jenner; J. W. Kebabian; D. R. Britton; M. P. De Ninno; J. R. Taylor; M. S. Lawrence; D. E. Redmond; R. J. Vermeulen; B. Drukarch; M. C R Sahadat; P. Sokoloff; B. Giros; M. P. Martres; J. C. Schwartz; D. Levesque; M. P. Martres; P. Sokoloff; M. Andrieux; R. Besancon; P. Sokoloff; B. Giros; M. P. Martres; P. J. Bedard; T. Di Paolo; P. Falardeau; M. R. Luquin; J. Laguna; J. A. Obeso; B. Gomez-Mancilla; P. J. Bedard; P. Blanchet; P. J. Bedard; D. R. Britton; A. R. Crossman; A. R. Crossman; P. Voorn; G. Roest; H. J. Groenewegen; C. R. Gerfen; T. M. Engber; Z. Susel; P. Jenner; P. Jenner; A. H V Schapira; C. D. Marsden; H. Saggu; J. Cooksey; D. Dexter; R. J. Marttila; H. Lorentz; U. K. Rinne; S. F. Marklund; R. Adolfsson; C. G. Gottfries; D. R. Rosen; T. Siddique; D. Patterson; I. Ceballos; M. Lafon; F. Javoy-Agid; A. Clow; T. Hussain; V. Glover; M. C. Carrillo; S. Kanai; M. Nokubo; A. Clow; C. Freestone; E. Lewis; D. L. Felten; S. Y. Felten; R. W. Fuller; T. Yoshikawa; Y. Minamiyama; Y. Naito; A. Ubeda; C. Montesinos; M. Paya

doi:10.1212/wnl.45.3_suppl_3.s6

The rationale for the use of dopamine agonists in parkinson's disease

Peter Jenner, J. C. Schwartz, N. Giros, M. P. Matres, D. R. Sibley, F. J. Monsma, P. Sokoloff, M. P. Martres, B. Giros, G. E. Martin, M. Williams, D. J. Pettibone, M. Nomoto, S. Stahl, P. Jenner, R. J. Coleman, K. W. Lange, N. P. Quinn, P. A. Loschmann, P. N. ChongM. Nomoto, P. E. Setler, H. M. Sarau, C. L. Zirkle, M. Nomoto, P. Jenner, C. D. Marsden, P. Barone, K. S. Bankiewicz, G. U. Corsini, M. Nomoto, P. Jenner, C. D. Marsden, A. Braun, G. Fabbrini, M. M. Mouradian, J. A. Temlett, P. N. Chong, W. H. Oertel, J. A. Temlett, N. P. Quinn, P. G. Jenner, J. W. Kebabian, D. R. Britton, M. P. De Ninno, J. R. Taylor, M. S. Lawrence, D. E. Redmond, R. J. Vermeulen, B. Drukarch, M. C R Sahadat, P. Sokoloff, B. Giros, M. P. Martres, J. C. Schwartz, D. Levesque, M. P. Martres, P. Sokoloff, M. Andrieux, R. Besancon, P. Sokoloff, B. Giros, M. P. Martres, P. J. Bedard, T. Di Paolo, P. Falardeau, M. R. Luquin, J. Laguna, J. A. Obeso, B. Gomez-Mancilla, P. J. Bedard, P. Blanchet, P. J. Bedard, D. R. Britton, A. R. Crossman, A. R. Crossman, P. Voorn, G. Roest, H. J. Groenewegen, C. R. Gerfen, T. M. Engber, Z. Susel, P. Jenner, P. Jenner, A. H V Schapira, C. D. Marsden, H. Saggu, J. Cooksey, D. Dexter, R. J. Marttila, H. Lorentz, U. K. Rinne, S. F. Marklund, R. Adolfsson, C. G. Gottfries, D. R. Rosen, T. Siddique, D. Patterson, I. Ceballos, M. Lafon, F. Javoy-Agid, A. Clow, T. Hussain, V. Glover, M. C. Carrillo, S. Kanai, M. Nokubo, A. Clow, C. Freestone, E. Lewis, D. L. Felten, S. Y. Felten, R. W. Fuller, T. Yoshikawa, Y. Minamiyama, Y. Naito, A. Ubeda, C. Montesinos, M. Paya

Neurology

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126 Scopus citations

Abstract

Experimental and clinical studies indicate that both dopamine D₂-like and D_1-like receptors are important in reversing the motor symptoms of Parkinson's disease, and therefore stimulation of both D₁ and D₂ receptors may be advantageous in its treatment. At present, the role of other receptor subtypes, such as the D (₃) receptor, remains unknown, although in primates the D₃ receptor might be of importance because it exists in significant amounts within the caudate-putamen. Both D₁ and D₂ agonists induce dyskinesias in drug-naive, MPTP-treated primates and provoke dyskinesias in levodopa-primed animals. D₁ agonists in low doses, however, might have antiparkinsonian effects without inducing dyskinesias, and on repeated administration perhaps can diminish the intensity of dyskinesias in levodopa-primed, MPTP-treated primates. The production of dyskinesias in Parkinson's disease might reflect an imbalance in the D_1-direct and D_2-indirect GABAergic output pathways from the caudate-putamen, which colocalize tachykinins and enkephalins, respectively. Destruction of the nigrostriatal pathway decreases the mRNA for substance P but elevates the mRNA for enkephalin. Treatment with levodopa reverses the decrease in substance P mRNA but has either a partial or no effect on mRNA for enkephalin. This suggests that levodopa treatment leads to a new imbalance between output from the striatum through the direct and indirect pathways. In contrast, dopamine agonists appear less able than levodopa to manipulate basal ganglia outflow. This might reflect their decreased ability to reverse parkinsonian motor deficits or the greater ability of levodopa to provoke dyskinesias. Dopamine agonist drugs also might exert neuroprotective actions. Pergolide, like selegiline, elevates superoxide dismutase activity in brain, decreases hydrogen peroxide formation from dopamine, and preserves nigral cells in aging rats. Bromocriptine, apomorphine, and other agonists also scavenge free radicals and show antioxidant activity, compared with the mainly pro-oxidant actions of levodopa.

Original language	English (US)
Pages (from-to)	S6-S12
Journal	Neurology
Volume	45
Issue number	3
DOIs	https://doi.org/10.1212/wnl.45.3_suppl_3.s6
State	Published - Mar 1995

ASJC Scopus subject areas

Clinical Neurology

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10.1212/wnl.45.3_suppl_3.s6

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Jenner, P., Schwartz, J. C., Giros, N., Matres, M. P., Sibley, D. R., Monsma, F. J., Sokoloff, P., Martres, M. P., Giros, B., Martin, G. E., Williams, M., Pettibone, D. J., Nomoto, M., Stahl, S., Jenner, P., Coleman, R. J., Lange, K. W., Quinn, N. P., Loschmann, P. A., ... Paya, M. (1995). The rationale for the use of dopamine agonists in parkinson's disease. Neurology, 45(3), S6-S12. https://doi.org/10.1212/wnl.45.3_suppl_3.s6

@article{26805c91a6e048808160e3003686e2a2,

title = "The rationale for the use of dopamine agonists in parkinson's disease",

abstract = "Experimental and clinical studies indicate that both dopamine D2-like and D1-like receptors are important in reversing the motor symptoms of Parkinson's disease, and therefore stimulation of both D1 and D2 receptors may be advantageous in its treatment. At present, the role of other receptor subtypes, such as the D (3) receptor, remains unknown, although in primates the D3 receptor might be of importance because it exists in significant amounts within the caudate-putamen. Both D1 and D2 agonists induce dyskinesias in drug-naive, MPTP-treated primates and provoke dyskinesias in levodopa-primed animals. D1 agonists in low doses, however, might have antiparkinsonian effects without inducing dyskinesias, and on repeated administration perhaps can diminish the intensity of dyskinesias in levodopa-primed, MPTP-treated primates. The production of dyskinesias in Parkinson's disease might reflect an imbalance in the D1-direct and D2-indirect GABAergic output pathways from the caudate-putamen, which colocalize tachykinins and enkephalins, respectively. Destruction of the nigrostriatal pathway decreases the mRNA for substance P but elevates the mRNA for enkephalin. Treatment with levodopa reverses the decrease in substance P mRNA but has either a partial or no effect on mRNA for enkephalin. This suggests that levodopa treatment leads to a new imbalance between output from the striatum through the direct and indirect pathways. In contrast, dopamine agonists appear less able than levodopa to manipulate basal ganglia outflow. This might reflect their decreased ability to reverse parkinsonian motor deficits or the greater ability of levodopa to provoke dyskinesias. Dopamine agonist drugs also might exert neuroprotective actions. Pergolide, like selegiline, elevates superoxide dismutase activity in brain, decreases hydrogen peroxide formation from dopamine, and preserves nigral cells in aging rats. Bromocriptine, apomorphine, and other agonists also scavenge free radicals and show antioxidant activity, compared with the mainly pro-oxidant actions of levodopa.",

author = "Peter Jenner and Schwartz, {J. C.} and N. Giros and Matres, {M. P.} and Sibley, {D. R.} and Monsma, {F. J.} and P. Sokoloff and Martres, {M. P.} and B. Giros and Martin, {G. E.} and M. Williams and Pettibone, {D. J.} and M. Nomoto and S. Stahl and P. Jenner and Coleman, {R. J.} and Lange, {K. W.} and Quinn, {N. P.} and Loschmann, {P. A.} and Chong, {P. N.} and M. Nomoto and Setler, {P. E.} and Sarau, {H. M.} and Zirkle, {C. L.} and M. Nomoto and P. Jenner and Marsden, {C. D.} and P. Barone and Bankiewicz, {K. S.} and Corsini, {G. U.} and M. Nomoto and P. Jenner and Marsden, {C. D.} and A. Braun and G. Fabbrini and Mouradian, {M. M.} and Temlett, {J. A.} and Chong, {P. N.} and Oertel, {W. H.} and Temlett, {J. A.} and Quinn, {N. P.} and Jenner, {P. G.} and Kebabian, {J. W.} and Britton, {D. R.} and {De Ninno}, {M. P.} and Taylor, {J. R.} and Lawrence, {M. S.} and Redmond, {D. E.} and Vermeulen, {R. J.} and B. Drukarch and Sahadat, {M. C R} and P. Sokoloff and B. Giros and Martres, {M. P.} and Schwartz, {J. C.} and D. Levesque and Martres, {M. P.} and P. Sokoloff and M. Andrieux and R. Besancon and P. Sokoloff and B. Giros and Martres, {M. P.} and Bedard, {P. J.} and {Di Paolo}, T. and P. Falardeau and Luquin, {M. R.} and J. Laguna and Obeso, {J. A.} and B. Gomez-Mancilla and Bedard, {P. J.} and P. Blanchet and Bedard, {P. J.} and Britton, {D. R.} and Crossman, {A. R.} and Crossman, {A. R.} and P. Voorn and G. Roest and Groenewegen, {H. J.} and Gerfen, {C. R.} and Engber, {T. M.} and Z. Susel and P. Jenner and P. Jenner and Schapira, {A. H V} and Marsden, {C. D.} and H. Saggu and J. Cooksey and D. Dexter and Marttila, {R. J.} and H. Lorentz and Rinne, {U. K.} and Marklund, {S. F.} and R. Adolfsson and Gottfries, {C. G.} and Rosen, {D. R.} and T. Siddique and D. Patterson and I. Ceballos and M. Lafon and F. Javoy-Agid and A. Clow and T. Hussain and V. Glover and Carrillo, {M. C.} and S. Kanai and M. Nokubo and A. Clow and C. Freestone and E. Lewis and Felten, {D. L.} and Felten, {S. Y.} and Fuller, {R. W.} and T. Yoshikawa and Y. Minamiyama and Y. Naito and A. Ubeda and C. Montesinos and M. Paya",

year = "1995",

month = mar,

doi = "10.1212/wnl.45.3_suppl_3.s6",

language = "English (US)",

volume = "45",

pages = "S6--S12",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "3",

}

Jenner, P, Schwartz, JC, Giros, N, Matres, MP, Sibley, DR, Monsma, FJ, Sokoloff, P, Martres, MP, Giros, B, Martin, GE, Williams, M, Pettibone, DJ, Nomoto, M, Stahl, S, Jenner, P, Coleman, RJ, Lange, KW, Quinn, NP, Loschmann, PA, Chong, PN, Nomoto, M, Setler, PE, Sarau, HM, Zirkle, CL, Nomoto, M, Jenner, P, Marsden, CD, Barone, P, Bankiewicz, KS, Corsini, GU, Nomoto, M, Jenner, P, Marsden, CD, Braun, A, Fabbrini, G, Mouradian, MM, Temlett, JA, Chong, PN, Oertel, WH, Temlett, JA, Quinn, NP, Jenner, PG, Kebabian, JW, Britton, DR, De Ninno, MP, Taylor, JR, Lawrence, MS, Redmond, DE, Vermeulen, RJ, Drukarch, B, Sahadat, MCR, Sokoloff, P, Giros, B, Martres, MP, Schwartz, JC, Levesque, D, Martres, MP, Sokoloff, P, Andrieux, M, Besancon, R, Sokoloff, P, Giros, B, Martres, MP, Bedard, PJ, Di Paolo, T, Falardeau, P, Luquin, MR, Laguna, J, Obeso, JA, Gomez-Mancilla, B, Bedard, PJ, Blanchet, P, Bedard, PJ, Britton, DR, Crossman, AR, Crossman, AR, Voorn, P, Roest, G, Groenewegen, HJ, Gerfen, CR, Engber, TM, Susel, Z, Jenner, P, Jenner, P, Schapira, AHV, Marsden, CD, Saggu, H, Cooksey, J, Dexter, D, Marttila, RJ, Lorentz, H, Rinne, UK, Marklund, SF, Adolfsson, R, Gottfries, CG, Rosen, DR, Siddique, T, Patterson, D, Ceballos, I, Lafon, M, Javoy-Agid, F, Clow, A, Hussain, T, Glover, V, Carrillo, MC, Kanai, S, Nokubo, M, Clow, A, Freestone, C, Lewis, E, Felten, DL, Felten, SY, Fuller, RW, Yoshikawa, T, Minamiyama, Y, Naito, Y, Ubeda, A, Montesinos, C & Paya, M 1995, 'The rationale for the use of dopamine agonists in parkinson's disease', Neurology, vol. 45, no. 3, pp. S6-S12. https://doi.org/10.1212/wnl.45.3_suppl_3.s6

TY - JOUR

T1 - The rationale for the use of dopamine agonists in parkinson's disease

AU - Jenner, Peter

AU - Schwartz, J. C.

AU - Giros, N.

AU - Matres, M. P.

AU - Sibley, D. R.

AU - Monsma, F. J.

AU - Sokoloff, P.

AU - Martres, M. P.

AU - Giros, B.

AU - Martin, G. E.

AU - Williams, M.

AU - Pettibone, D. J.

AU - Nomoto, M.

AU - Stahl, S.

AU - Jenner, P.

AU - Coleman, R. J.

AU - Lange, K. W.

AU - Quinn, N. P.

AU - Loschmann, P. A.

AU - Chong, P. N.

AU - Nomoto, M.

AU - Setler, P. E.

AU - Sarau, H. M.

AU - Zirkle, C. L.

AU - Nomoto, M.

AU - Jenner, P.

AU - Marsden, C. D.

AU - Barone, P.

AU - Bankiewicz, K. S.

AU - Corsini, G. U.

AU - Nomoto, M.

AU - Jenner, P.

AU - Marsden, C. D.

AU - Braun, A.

AU - Fabbrini, G.

AU - Mouradian, M. M.

AU - Temlett, J. A.

AU - Chong, P. N.

AU - Oertel, W. H.

AU - Temlett, J. A.

AU - Quinn, N. P.

AU - Jenner, P. G.

AU - Kebabian, J. W.

AU - Britton, D. R.

AU - De Ninno, M. P.

AU - Taylor, J. R.

AU - Lawrence, M. S.

AU - Redmond, D. E.

AU - Vermeulen, R. J.

AU - Drukarch, B.

AU - Sahadat, M. C R

AU - Sokoloff, P.

AU - Giros, B.

AU - Martres, M. P.

AU - Schwartz, J. C.

AU - Levesque, D.

AU - Martres, M. P.

AU - Sokoloff, P.

AU - Andrieux, M.

AU - Besancon, R.

AU - Sokoloff, P.

AU - Giros, B.

AU - Martres, M. P.

AU - Bedard, P. J.

AU - Di Paolo, T.

AU - Falardeau, P.

AU - Luquin, M. R.

AU - Laguna, J.

AU - Obeso, J. A.

AU - Gomez-Mancilla, B.

AU - Bedard, P. J.

AU - Blanchet, P.

AU - Bedard, P. J.

AU - Britton, D. R.

AU - Crossman, A. R.

AU - Voorn, P.

AU - Roest, G.

AU - Groenewegen, H. J.

AU - Gerfen, C. R.

AU - Engber, T. M.

AU - Susel, Z.

AU - Jenner, P.

AU - Schapira, A. H V

AU - Marsden, C. D.

AU - Saggu, H.

AU - Cooksey, J.

AU - Dexter, D.

AU - Marttila, R. J.

AU - Lorentz, H.

AU - Rinne, U. K.

AU - Marklund, S. F.

AU - Adolfsson, R.

AU - Gottfries, C. G.

AU - Rosen, D. R.

AU - Siddique, T.

AU - Patterson, D.

AU - Ceballos, I.

AU - Lafon, M.

AU - Javoy-Agid, F.

AU - Clow, A.

AU - Hussain, T.

AU - Glover, V.

AU - Carrillo, M. C.

AU - Kanai, S.

AU - Nokubo, M.

AU - Clow, A.

AU - Freestone, C.

AU - Lewis, E.

AU - Felten, D. L.

AU - Felten, S. Y.

AU - Fuller, R. W.

AU - Yoshikawa, T.

AU - Minamiyama, Y.

AU - Naito, Y.

AU - Ubeda, A.

AU - Montesinos, C.

AU - Paya, M.

PY - 1995/3

Y1 - 1995/3

N2 - Experimental and clinical studies indicate that both dopamine D2-like and D1-like receptors are important in reversing the motor symptoms of Parkinson's disease, and therefore stimulation of both D1 and D2 receptors may be advantageous in its treatment. At present, the role of other receptor subtypes, such as the D (3) receptor, remains unknown, although in primates the D3 receptor might be of importance because it exists in significant amounts within the caudate-putamen. Both D1 and D2 agonists induce dyskinesias in drug-naive, MPTP-treated primates and provoke dyskinesias in levodopa-primed animals. D1 agonists in low doses, however, might have antiparkinsonian effects without inducing dyskinesias, and on repeated administration perhaps can diminish the intensity of dyskinesias in levodopa-primed, MPTP-treated primates. The production of dyskinesias in Parkinson's disease might reflect an imbalance in the D1-direct and D2-indirect GABAergic output pathways from the caudate-putamen, which colocalize tachykinins and enkephalins, respectively. Destruction of the nigrostriatal pathway decreases the mRNA for substance P but elevates the mRNA for enkephalin. Treatment with levodopa reverses the decrease in substance P mRNA but has either a partial or no effect on mRNA for enkephalin. This suggests that levodopa treatment leads to a new imbalance between output from the striatum through the direct and indirect pathways. In contrast, dopamine agonists appear less able than levodopa to manipulate basal ganglia outflow. This might reflect their decreased ability to reverse parkinsonian motor deficits or the greater ability of levodopa to provoke dyskinesias. Dopamine agonist drugs also might exert neuroprotective actions. Pergolide, like selegiline, elevates superoxide dismutase activity in brain, decreases hydrogen peroxide formation from dopamine, and preserves nigral cells in aging rats. Bromocriptine, apomorphine, and other agonists also scavenge free radicals and show antioxidant activity, compared with the mainly pro-oxidant actions of levodopa.

AB - Experimental and clinical studies indicate that both dopamine D2-like and D1-like receptors are important in reversing the motor symptoms of Parkinson's disease, and therefore stimulation of both D1 and D2 receptors may be advantageous in its treatment. At present, the role of other receptor subtypes, such as the D (3) receptor, remains unknown, although in primates the D3 receptor might be of importance because it exists in significant amounts within the caudate-putamen. Both D1 and D2 agonists induce dyskinesias in drug-naive, MPTP-treated primates and provoke dyskinesias in levodopa-primed animals. D1 agonists in low doses, however, might have antiparkinsonian effects without inducing dyskinesias, and on repeated administration perhaps can diminish the intensity of dyskinesias in levodopa-primed, MPTP-treated primates. The production of dyskinesias in Parkinson's disease might reflect an imbalance in the D1-direct and D2-indirect GABAergic output pathways from the caudate-putamen, which colocalize tachykinins and enkephalins, respectively. Destruction of the nigrostriatal pathway decreases the mRNA for substance P but elevates the mRNA for enkephalin. Treatment with levodopa reverses the decrease in substance P mRNA but has either a partial or no effect on mRNA for enkephalin. This suggests that levodopa treatment leads to a new imbalance between output from the striatum through the direct and indirect pathways. In contrast, dopamine agonists appear less able than levodopa to manipulate basal ganglia outflow. This might reflect their decreased ability to reverse parkinsonian motor deficits or the greater ability of levodopa to provoke dyskinesias. Dopamine agonist drugs also might exert neuroprotective actions. Pergolide, like selegiline, elevates superoxide dismutase activity in brain, decreases hydrogen peroxide formation from dopamine, and preserves nigral cells in aging rats. Bromocriptine, apomorphine, and other agonists also scavenge free radicals and show antioxidant activity, compared with the mainly pro-oxidant actions of levodopa.

UR - http://www.scopus.com/inward/record.url?scp=0029269229&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029269229&partnerID=8YFLogxK

U2 - 10.1212/wnl.45.3_suppl_3.s6

DO - 10.1212/wnl.45.3_suppl_3.s6

M3 - Article

C2 - 7715795

AN - SCOPUS:0029269229

SN - 0028-3878

VL - 45

SP - S6-S12

JO - Neurology

JF - Neurology

IS - 3

ER -

The rationale for the use of dopamine agonists in parkinson's disease

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