Abstract：
:Levodopa is the standard-of-care for Parkinson's disease, but continued loss of dopamine neurons with disease progression decreases its bioconversion to dopamine, leading to increased side effects and decreased efficacy. In theory, dopamine agonists could equal levodopa, but no approved oral "dopamine agonist" matches the efficacy of levodopa. There are consistent data in both primate models and in Parkinson's disease showing that selective high intrinsic activity D1 agonists can equal levodopa in efficacy. There are, however, no data on whether such compounds would be effective in severe disease when levodopa efficacy is low or absent. We compared two approved antiparkinson drugs (levodopa and the D2/3 agonist bromocriptine) with the experimental selective D1 full agonist dihydrexidine in two severely parkinsonian MPTP-treated non-human primates. Bromocriptine caused no discernible improvement in parkinsonian signs, whereas levodopa caused a small transient improvement in one of the two subjects. Conversely, the full D1 agonist dihydrexidine caused a dramatic improvement in both subjects, decreasing parkinsonian signs by ca. 75%. No attenuation of dihydrexidine effects was observed when the two subjects were pretreated with the D2 antagonist remoxipride. These data provide evidence that selective D1 agonists may provide profound antiparkinson symptomatic relief even when the degree of nigrostriatal degeneration is so severe that current drugs are ineffective. Until effective disease-modifying therapies are discovered, high intrinsic activity D1 agonists may offer a major therapeutic advance in improving the quality of life, and potentially the longevity, of late stage Parkinson's patients.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Mailman RB,Yang Y,Huang Xdoi
10.1016/j.ejphar.2020.173760subject
Has Abstractpub_date
2021-02-05 00:00:00pages
173760eissn
0014-2999issn
1879-0712pii
S0014-2999(20)30852-9journal_volume
892pub_type
杂志文章abstract：:To investigate the long-term functional change in the 5-HT(2A) receptor after acute stress, we examined the effect of single footshock on head shake behavior induced by the 5-HT(2A) receptor agent (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) in rats. Head shakes were evoked in a dose-dependent manner by 0...
journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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doi：10.1016/0014-2999(78)90163-2
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abstract：:Meperidine has atypical opioid receptor agonist effects and shares some structural features with the phenyltropane (WIN) analogs of cocaine. In combination with 0.1 mg/kg naltrexone, meperidine produced cocaine-like discriminative stimulus effects in monkeys, whereas morphine was inactive. Both cocaine and meperidine ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1996-02-15 00:00:00
abstract：:The antagonist effects of ketanserin and 2'-methyl-4'-(5-methyl-1,2,4)oxadiazol-3-yl)-biphenyl-[4-carboxyli c acid 4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR 127,935) were compared to naratriptan-induced inhibition of cAMP formation in C6-glial cell lines stably expressing human 5-HT1D or 5-HT1B receptor ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1996-04-04 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.07.015
更新日期：2016-10-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.07.112
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1985-11-19 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90261-8
更新日期：1982-09-24 00:00:00
abstract：:Electrical field stimulation of the isolated adventitial and intima-medial layers of rabbit aorta preloaded with 3H-noradrenaline elicited a 3H outflow. The initial 3H outflow from adventitia was independent of external Ca2+ concentration. Each of the subsequent 3H outflows was mainly Ca2+ sensitive. All stimulation-i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90156-4
更新日期：1976-10-01 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：2020-12-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.10.044
更新日期：2012-01-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90234-0
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.07.046
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.08.048
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.04.005
更新日期：2004-06-16 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
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更新日期：2019-12-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90499-0
更新日期：1984-08-17 00:00:00
abstract：:In the present study we investigated the in vivo pharmacological profile of the benz[e]indole cis-8-hydroxy-3-(n-propyl)],2,3a,4,5,9b-hexahydro-1H-benz[e]indole (cis-8-OH-PBZI), which has been described as a preferential dopamine D3 receptor agonist in vitro. The compound inhibited spontaneous locomotor activity in mi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01494-5
更新日期：1998-01-26 00:00:00
