Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Neural Transm (Vienna). 2024 Sep 11. doi: 10.1007/s00702-024-02825-8. Online
 ahead of print.

Dopamine agonists in the treatment of Parkinson's disease: the show must go on.

Jost WH(1).

Author information:
(1)Parkinson-Klinik Ortenau, Kreuzbergstr. 12-16, 77723, Wolfach, Germany. 
w.jost@parkinson-klinik.de.

Dopamine agonists (DA) have proven very successful in the treatment of 
Parkinson's disease for a good many years now. In the 1990's they experienced a 
high level of acceptance particularly in the European countries because their 
efficacy was in fact established, their tolerability was improved on and, in 
addition, several preparations were available with longer effect durations. But 
the discovery of cardiac fibroses led to a substantial setback and even 
rejection of therapy using ergoline DA. In recent years, impulse control 
disturbances have been observed increasingly with the result that higher doses 
have been reduced and the previously popular use of non-ergoline DA was 
discontinued. In addition, newer data on levodopa were published which clearly 
relativized the occurrence of late complications under levodopa and led to a 
differentiated use. Thus the importance of their use has waned over the years. 
But we should rather avoid repeating the mistakes of the past. DA serve us well 
and reliably so. The pendulum apparently thrives of the extremes but in the case 
of DA we should keep from falling back into the other extreme: We can and in 
fact must further make use of the DA, but with a clear view of specific goals 
and in a differentiated way. DA constitute the second-most important substance 
class after levodopa. Their optimized application can only be recommended for 
the good of our patients.

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, 
part of Springer Nature.

DOI: 10.1007/s00702-024-02825-8
PMID: 39261330


2. J Neurol. 2024 Aug 29. doi: 10.1007/s00415-024-12632-6. Online ahead of print.

Pharmacotherapy of motor symptoms in early and mid-stage Parkinson's disease: 
guideline "Parkinson's disease" of the German Society of Neurology.

Höllerhage M(1), Becktepe J(2), Classen J(3), Deuschl G(2), Ebersbach G(4), 
Hopfner F(5), Lingor P(6)(7)(8), Löhle M(9)(10), Maaß S(8), Pötter-Nerger M(11), 
Odin P(12)(13), Woitalla D(14); German Parkinson’s Guidelines Group; Trenkwalder 
C(15)(16), Höglinger GU(17)(18)(19).

Collaborators: Bähr M, Berg D, Brockmann K, Buhmann C, Ceballos-Baumann A, 
Claßen J, Deuschl C, Dodel R, Eggers C, van Eimeren T, Fanciulli A, Fimm B, 
Folkerts AK, Gausepohl M, Hasan A, Hermann W, Hilker-Roggendorf R, Höglinger G, 
Jost W, Kalbe E, Kassubek J, Klebe S, Klein C, Klietz M, Köglsperger T, Kühn A, 
Krack P, Krismer F, Kuhlenbäumer G, Levin J, Liepelt-Scarfone I, Loewenbrück K, 
Lorenzl S, Maetzler W, Menzel R, Meyer PT, Mollenhauer B, Neumann M, Outeiro T, 
Reese R, Reetz K, Rieß O, Ruf V, Schneider A, Schrader C, Schnitzler A, Seppi K, 
Sixel-Döring F, Storch A, Tönges L, van Eimeren T, Walter U, Wächter T, Warnecke 
T, Wegner F, Winkler C, Witt K, Zeuner K.

Author information:
(1)Department of Neurology, Hannover Medical School, Hannover, Germany.
(2)Department of Neurology, Christian-Albrechts-University, Kiel, Germany.
(3)Department of Neurology, Leipzig University Medical Center, Leipzig, Germany.
(4)Movement Disorders Hospital, Beelitz-Heilstätten, Germany.
(5)Department of Neurology with Friedrich Baur Institute, LMU University 
Hospital, Ludwig-Maximilians-Universität (LMU) München, Marchioninistr. 15, 
81377, Munich, Germany.
(6)School of Medicine and Health, Department of Neurology, Technical University 
of Munich, Klinikum rechts der Isar, Munich, Germany.
(7)Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
(8)German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
(9)Department of Neurology, University of Rostock, 18051, Rostock, Germany.
(10)Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) 
Rostock/Greifswald, Rostock, Germany.
(11)Department of Neurology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, 
Germany.
(12)Division of Neurology, Lund University, Lund, Sweden.
(13)Department of Neurology, Skåne University Hospital, Lund, Sweden.
(14)Department of Neurology, St. Josef-Hospital, Katholische Kliniken 
Ruhrhalbinsel, Contilia Gruppe, Essen, Germany.
(15)Paracelsus-Elena-Klinik, Kassel, Germany.
(16)Department of Neurosurgery, University Medical Center, Göttingen, Germany.
(17)Department of Neurology with Friedrich Baur Institute, LMU University 
Hospital, Ludwig-Maximilians-Universität (LMU) München, Marchioninistr. 15, 
81377, Munich, Germany. Guenter.Hoeglinger@med.uni-muenchen.de.
(18)Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. 
Guenter.Hoeglinger@med.uni-muenchen.de.
(19)German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. 
Guenter.Hoeglinger@med.uni-muenchen.de.

BACKGROUND AND OBJECTIVE: There are multiple pharmacological treatment options 
for motor symptoms of Parkinson's disease (PD). These comprise multiple drug 
classes which are approved for the condition, including levodopa, dopamine 
agonists, COMT inhibitors, MAO-B inhibitors, NMDA-receptor antagonists, 
anticholinergics, and others. Some of the drugs are approved for monotherapy and 
combination therapy while others are only approved as adjunctive therapy to 
levodopa. Furthermore, treatment for special treatment situations, e.g., rescue 
medication for off-phases, for tremor, treatment during pregnancy and breast 
feeding is discussed and recommendations are given with further details.
METHODS: The recommendations were based on systematic literature reviews, 
drafted by expert teams, consented in online polls followed by online consensus 
meetings of the whole German Parkinson's Guideline Group, and publicly released 
in November 2023.
RESULTS: In the new S2k (i.e., consensus-based) guidelines, the pharmacotherapy 
of the motor symptoms of PD is discussed in five chapters. These comprise 
"Parkinson medication", "Initial monotherapy", "Early combination therapy", 
"Fluctuations and dyskinesia", and "Parkinsonian tremor". Furthermore, there is 
a chapter for special treatment situations, including perioperative management, 
freezing of gait, and pregnancy and breastfeeding.
CONCLUSION: The recommendations for the pharmacotherapy of motor symptoms of PD 
have been updated. Newly available drugs have been added, while other drugs 
(e.g., ergoline dopamine agonists, anticholinergics, budipine) have been removed 
from the recommendations.

© 2024. The Author(s).

DOI: 10.1007/s00415-024-12632-6
PMID: 39207521


3. Neuron. 2024 Oct 9;112(19):3295-3310.e8. doi: 10.1016/j.neuron.2024.07.003.
Epub  2024 Aug 1.

Structural basis of psychedelic LSD recognition at dopamine D(1) receptor.

Fan L(1), Zhuang Y(2), Wu H(3), Li H(4), Xu Y(2), Wang Y(2), He L(3), Wang S(5), 
Chen Z(3), Cheng J(4), Xu HE(6), Wang S(7).

Author information:
(1)Key Laboratory of Systems Health Science of Zhejiang Province, School of Life 
Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of 
Sciences, Hangzhou 310024, China. Electronic address: fanluyu2018@sibcb.ac.cn.
(2)State Key Laboratory of Drug Research, Center for Structure and Function of 
Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 
Shanghai 201203, China.
(3)Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and 
Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy 
of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
(4)iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of 
Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
(5)Laboratory of Anesthesia and Critical Care Medicine in Colleges and 
Universities of Shandong Province, School of Anesthesiology, Shandong Second 
Medical University, Weifang 261021, China.
(6)State Key Laboratory of Drug Research, Center for Structure and Function of 
Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 
Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 
100049, China; Lingang Laboratory, Shanghai 200031, China. Electronic address: 
eric.xu@simm.ac.cn.
(7)Key Laboratory of Systems Health Science of Zhejiang Province, School of Life 
Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of 
Sciences, Hangzhou 310024, China; Key Laboratory of Multi-Cell Systems, Shanghai 
Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular 
Cell Science, Chinese Academy of Sciences, University of Chinese Academy of 
Sciences, Shanghai 200031, China. Electronic address: wangsheng@sibcb.ac.cn.

Understanding the kinetics of LSD in receptors and subsequent induced signaling 
is crucial for comprehending both the psychoactive and therapeutic effects of 
LSD. Despite extensive research on LSD's interactions with serotonin 2A and 2B 
receptors, its behavior on other targets, including dopamine receptors, has 
remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound 
dopamine D1 receptor (DRD1)-legobody complexes, accompanied by a 
β-arrestin-mimicking nanobody, NBA3, shedding light on the determinants of G 
protein coupling versus β-arrestin coupling. Structural analysis unveils a 
distinctive binding mode of LSD in DRD1, particularly with the ergoline moiety 
oriented toward TM4. Kinetic investigations uncover an exceptionally rapid 
dissociation rate of LSD in DRD1, attributed to the flexibility of extracellular 
loop 2 (ECL2). Moreover, G protein can stabilize ECL2 conformation, leading to a 
significant slowdown in ligand's dissociation rate. These findings establish a 
solid foundation for further exploration of G protein-coupled receptor (GPCR) 
dynamics and their relevance to signal transduction.

Copyright © 2024 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.neuron.2024.07.003
PMID: 39094559 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of interests The authors declare no 
competing interests.


4. Drug Test Anal. 2024 Jul 4. doi: 10.1002/dta.3767. Online ahead of print.

Analytical and behavioral characterization of 1-hexanoyl-LSD (1H-LSD).

Brandt SD(1), Kavanagh PV(2), Gare S(3), Stratford A(4), Halberstadt 
AL(5)(6)(7).

Author information:
(1)School of Pharmacy and Biomolecular Sciences, Liverpool John Moores 
University, Liverpool, UK.
(2)Department of Pharmacology and Therapeutics, School of Medicine, Trinity 
Centre for Health Sciences, St. James Hospital, Dublin, Ireland.
(3)Department of Chemistry, School of Physical Sciences, University of 
Liverpool, Liverpool, UK.
(4)Synex Synthetics BV, Maastricht, The Netherlands.
(5)Department of Psychiatry, University of California San Diego, San Diego, 
Southern California, USA.
(6)Center for Psychedelic Research, University of California San Diego, San 
Diego, Southern California, USA.
(7)Research Service, VA San Diego Healthcare System, San Diego, Southern 
California, USA.

The development of lysergic acid diethylamide (LSD) derivatives and analogs 
continues to inform the design of novel receptor probes and potentially new 
medicines. On the other hand, a number of newly developed LSD derivatives have 
also emerged as recreational drugs, leading to reports of their detection in 
some countries. One position in the ergoline scaffold of LSD that is frequently 
targeted is the N1-position; numerous N1-alkylcarbonyl LSD derivatives have been 
reported where the acyl chain is attached to the indole nitrogen, for example, 
in the form of linear n-alkane substituents, which represent higher homologs of 
the prototypical 1-acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52). In this 
study, 1-hexanoyl-LSD (1H-LSD, SYN-L-027), a novel N1-acyl LSD derivative, was 
characterized analytically using standard techniques, followed by evaluation of 
its in vivo behavioral effects using the mouse head-twitch response (HTR) assay 
in C57BL/6J mice. 1H-LSD induced the HTR, with a median effective dose (ED50) of 
192.4 μg/kg (equivalent to 387 nmol/kg), making it roughly equipotent to ALD-52 
when tested previously under similar conditions. Similar to other N1-acylated 
analogs, 1H-LSD is anticipated to by hydrolyzed to LSD in vivo and acts as a 
prodrug. It is currently unknown whether 1H-LSD has appeared as on the research 
chemical market or is being used recreationally.

© 2024 The Author(s). Drug Testing and Analysis published by John Wiley & Sons 
Ltd.

DOI: 10.1002/dta.3767
PMID: 38965834


5. Cabergoline.

Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National 
Institute of Child Health and Human Development; 2006–.
2024 May 15.

Cabergoline is usually not used during breastfeeding because it suppresses 
lactation. The U.S. Food and Drug Administration considers cabergoline to be not 
indicated to suppress lactation because the similar drug bromocriptine has 
caused hypertension, stroke, seizures and psychosis when used for this purpose. 
However, two systematic reviews found that cabergoline was generally well 
tolerated for use in suppressing lactation, but dizziness, headache, nausea and 
vomiting occur occasionally.[1-3] A retrospective study of 225 women who 
received cabergoline postpartum had a maximum decrease in systolic blood 
pressure of 10.88 mm Hg at 20 to 24 hours after the dose.[4] Serious reactions 
are uncommon, but include thromboembolic and neurologic events. Psychiatric 
symptoms have occurred rarely. Some experts recommend cabergoline as a safer 
alternative to bromocriptine for lactation suppression, but others do not.[5-9] 
The disadvantage of cabergoline is that it has a half-life of about 68 hours, 
which means that any adverse effects might persist for a prolonged period of 
time. Women treated with cabergoline for pituitary adenomas who become pregnant 
can breastfed their infants with no apparent risk of recurrence. A treatment 
scheme has been reported for mothers with hypergalactia that uses low doses of 
cabergoline to decrease milk supply.[10] Decreased milk synthesis may occur by 2 
days after drug administration.[11]

PMID: 30000386