Lisuride: Difference between revisions

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== Mode of action ==
== Mode of action ==


Lisuride is a dopamine agonist.
Lisuride is a dopamine and serotonin receptor [[partial agonist]].  It has a high affinity for the dopamine D2, D3 and D4 receptors, as well as serotonin 5-HT1A<ref name="pmid12373423">{{cite journal |author=Marona-Lewicka D, Kurrasch-Orbaugh DM, Selken JR, Cumbay MG, Lisnicchia JG, Nichols DE |title=Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats |journal=Psychopharmacology (Berl.) |volume=164 |issue=1 |pages=93–107 |date=October 2002 |pmid=12373423 |doi=10.1007/s00213-002-1141-z |url=}}</ref> and 5-HT2A/C receptors.<ref name="pmid9600588">{{cite journal |author=Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M |title=Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors |journal=Psychopharmacology (Berl.) |volume=136 |issue=4 |pages=409–14 |date=April 1998 |pmid=9600588 |doi=10.1007/s002130050585 |url=}}</ref>  While lisuride has a similar receptor binding profile to the more well-known and chemically similar ergoloid N,N-diethyl-lysergamide ([[LSD]]) and inhibits dorsal raphe serotonergic neurons in a similar fashion to LSD,<ref name="pmid470543">{{cite journal |author=Rogawski MA, Aghajanian GK |title= Response of central monoaminergic neurons to
lisuride: comparison with LSD |journal= Life Sci.|year= 1979| volume= 24 |issue=14| pages= 1289–1297 |pmid= 470543}}</ref> it lacks the [[psychedelic]] effects of its sister compound. It has been suggested that this may be because lisuride acts as an agonist at 5-HT1A and 5-HT2A subtypes but behaves as an antagonist at 5-HT2C, inhibiting the psychedelic effect.<ref>{{Cite doi|10.1016/j.pharmthera.2003.11.002}}</ref> Newer findings suggest that the lack of psychedelic action arises from the phenomenon of [[functional selectivity|biased agonism]]. Stimulation of the 5-HT2A protomer within the [[5-HT2A receptor|5-HT2A]]-[[Glutamate receptor#Metabotropic glutamate receptors|mGlu2]] receptor complex evokes psychedelic effects, while these effects do not occur during sole stimulation of monomeric 5-HT2A receptors. Accordingly, different [[G-protein]]s are involved.<ref>{{cite journal |author=Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J |title=Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists |journal=Neurosci. Lett. |volume=493 |issue=3 |pages=76–9 |year=2011 |pmid=21276828 |pmc=3064746 |doi=10.1016/j.neulet.2011.01.046 |url=http://linkinghub.elsevier.com/retrieve/pii/S0304-3940(11)00092-9}}</ref><ref>{{cite journal |author=González-Maeso J, Ang RL, Yuen T, ''et al.'' |title=Identification of a serotonin/glutamate receptor complex implicated in psychosis |journal=Nature |volume=452 |issue=7183 |pages=93–7 |year=2008 |pmid=18297054 |pmc=2743172 |doi=10.1038/nature06612 |url=http://dx.doi.org/10.1038/nature06612}}</ref> Lisurid behaves as an agonist at the 5-HT2AR monomer. Since it competitively antagonises the effects of LSD, it may be regarded as a protomer antagonist of the 5-HT2A-mGluR heteromer.<ref>González-Maeso J ''et al.'' (2007): "Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior", ''Neuron'', Bd. 53, S. 439. PMID 17270739</ref> GPCR oligomers are discrete entities and usually possess properties distinct from their parent monomeric receptors.


== Commercial names ==
== Commercial names ==

Revision as of 04:57, 7 February 2014

Lisuride
Clinical data
Routes of
administration		Oral, subcutaneous, transdermal
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability10-20% for lisuride hydrogenmaleate
Protein bindingabout 15%
MetabolismHepatic
Elimination half-life2 hours
Excretionrenal and biliary in equal amounts
Identifiers
CAS Number
PubChem CID
DrugBank
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC20H26N4O
Molar mass338.447 g/mol

Lisuride (brand name in Germany Dopergin) is an anti-Parkinson's drug of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base (see table on the right) and as hydrogenmaleate salt.

Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks. The use of lisuride as initial anti-Parkinsonian treatment has been advocated, delaying the need for levodopa until lisuride becomes insufficient for controlling the Parkinsonian disability. Preliminary trials suggest that the dermal application of lisuride may be useful in the treatment of Parkinson's disease. Lisuride is not currently available in the US.

Mode of action

Lisuride is a dopamine and serotonin receptor partial agonist. It has a high affinity for the dopamine D2, D3 and D4 receptors, as well as serotonin 5-HT1A[1] and 5-HT2A/C receptors.[2] While lisuride has a similar receptor binding profile to the more well-known and chemically similar ergoloid N,N-diethyl-lysergamide (LSD) and inhibits dorsal raphe serotonergic neurons in a similar fashion to LSD,[3] it lacks the psychedelic effects of its sister compound. It has been suggested that this may be because lisuride acts as an agonist at 5-HT1A and 5-HT2A subtypes but behaves as an antagonist at 5-HT2C, inhibiting the psychedelic effect.[4] Newer findings suggest that the lack of psychedelic action arises from the phenomenon of biased agonism. Stimulation of the 5-HT2A protomer within the 5-HT2A-mGlu2 receptor complex evokes psychedelic effects, while these effects do not occur during sole stimulation of monomeric 5-HT2A receptors. Accordingly, different G-proteins are involved.[5][6] Lisurid behaves as an agonist at the 5-HT2AR monomer. Since it competitively antagonises the effects of LSD, it may be regarded as a protomer antagonist of the 5-HT2A-mGluR heteromer.[7] GPCR oligomers are discrete entities and usually possess properties distinct from their parent monomeric receptors.

Commercial names

Name Country of Use
Arolac France
Cuvalit Germany
Dipergon Greece
Dopergin(e) Germany, Spain, France, China
Dopergine Belgium
Lysenyl Forte Czech Republic, Slovakia
Prolacam Australia
Revanil UK

History

Synthesis of lisuride was first described in 1960.

Indications

See also

Template:Ergolines Template:Antimigraine preparations Template:Dopamine agonists

de:Lisurid

  1. ↑ Marona-Lewicka D, Kurrasch-Orbaugh DM, Selken JR, Cumbay MG, Lisnicchia JG, Nichols DE (October 2002). "Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats". Psychopharmacology (Berl.). 164 (1): 93–107. doi:10.1007/s00213-002-1141-z. PMID 12373423.
  2. ↑ Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M (April 1998). "Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors". Psychopharmacology (Berl.). 136 (4): 409–14. doi:10.1007/s002130050585. PMID 9600588.
  3. ↑ Rogawski MA, Aghajanian GK (1979). "Response of central monoaminergic neurons to lisuride: comparison with LSD". Life Sci. 24 (14): 1289–1297. PMID 470543. line feed character in |title= at position 45 (help)
  4. ↑ Template:Cite doi
  5. ↑ Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J (2011). "Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists". Neurosci. Lett. 493 (3): 76–9. doi:10.1016/j.neulet.2011.01.046. PMC 3064746. PMID 21276828.
  6. ↑ González-Maeso J, Ang RL, Yuen T; et al. (2008). "Identification of a serotonin/glutamate receptor complex implicated in psychosis". Nature. 452 (7183): 93–7. doi:10.1038/nature06612. PMC 2743172. PMID 18297054.
  7. ↑ González-Maeso J et al. (2007): "Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior", Neuron, Bd. 53, S. 439. PMID 17270739
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