Reseptoritaso, jossa LSD vaikuttaa ihmiseen

LÄHDE: Psychopharmacology (Berl). 2010 Feb;208(2):179-89. Epub 2009 Nov 25. LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT(2A) receptor. Halberstadt AL, Geyer MA. Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.

Tiivistelmä (Abstract)

RATIONALE: Compounds that activate the 5-HT(2A) receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans.

Sellaiset yhdisteet, jotka aktivoivat ihmisen 5-HT(2A) reseptorin , kuten LSD, vaikuttavat hallusinaatioita muodostavasti ihmisessä.

Eräänä merkittävänä poikkeuksena on lisuridi- molekyyli vaikka se on aika tavalla LSD:n kaltainen rakenne. Sillä ei ole hallusinogeenistä vaikutusta, vaikka se kuitenkin on tehokas 5-HT(2A) reseptorin myötävaikuttaja.

One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT(2A) agonist.

LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of sensorimotor gating, by activating 5-HT(2A) receptors in rats.

On osoittautunut, että LSD ja muut hallusinogeenit katkaisevat PPI:n , prepulsorisen inhibition, joka on sensorimotorisen jonikanavatoiminnan operatiivinen mittari, ja sen ne tekevät aktivoimalla 5-HT(2A) reseptorin ( koe-eläimenä on rotta).

OBJECTIVE: We tested whether lisuride disrupts PPI in male Sprague-Dawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD.

Tutkijat testasivat myös, jos lisuridi katkaisee prepulsatorisen estymisen koe-eläimessä. Tehtiin myös kokeita lisuridivasteen mekanismin selvittämiseksi tämän prepulsatorisen inhibition suhteen ja verrattiin lisuridin ja LSD:n vaikutuksia.

RESULTS: Confirming a previous report, LSD (0.05, 0.1, and 0.2 mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT(2A) antagonist MDL11,939.

Aiemmat raportit vahvistettiin: LSD madalsi prepulsatorista inhibitiota ja LSD:n vaikutus taas saatiin blokeerattua antamalla esikäsittelynä selektiivistä 5-HT(2A) antagonistia MDL. vaikuttama

Administration of lisuride (0.0375, 0.075, and 0.15 mg/kg, s.c.) also reduced PPI.

However, the PPI disruption induced by lisuride (0.075 mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT(1A) antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D(2)/D(3) receptor antagonist raclopride (0.1 mg/kg, s.c).

Lisuridin anto myös indusoi PPI:n aleneman, mutta tämä ei ollut blokeerattavissa mainitulla reseptoriantagonistilla MDL11,939 tai selektiivisellä 5-HT(1A) antagonistilla WAY-100635. Mutta sen sijaan voitiin estää preventiivisesti esikäsittelemällä selektiivisellä D(2)/D(3) reseptoriantagonistilla raclopridillä.

CONCLUSIONS: The effect of LSD on PPI is mediated by the 5-HT(2A) receptor, whereas activation of the 5-HT(2A) receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT(2A) agonist.

JOHTOPÄÄTÖS: LSD:n vaikutus prepulsatoriseen inhibitioon välittyy 5-HT(2A) reseptoriteitse, kun taas 5-HT(2A) reseptorin aktivaatio ei vaikuta osallistuvan lisuridin tekemiin PPI-vaikutuksiin. Nämä tutkimukset osoittavat että lisuridi ja LSD keskeyttävät PP-inhibition erilaisilla reseptorimekanismeilla ja täten tukevat sitä käsitystä, että lisuridi voidaan luokitella non-hallusinogeeniseksi 5-HT(2A) agonistiksi.

• Mikä on tämä LISURIDI?

Wikipedia antaa valoa. se on lääkeaineena käytetty juuri reseptoritason loogiikkaan perustaen antiparkinson aineena.

Lisuride (Dopergin, Proclacam, Revanil) is an antiparkinson agent 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. As lisuride is very poorly absorbed when take orally and has a short half-life, continuous transdermal administration offers significant advantages and could make the compound a far more consistent therapeutic. Lisuride is not currently available in the US, as the drug was not a commercial success in comparison with other dopamine receptor agonist anti-parkinsonian compounds. It is still used clinically in a number of countries in the EU and is still commercially available in the UK and China.

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 and 5-HT2A/C receptors. While lisuride has a similar receptor binding profile to the more well-known and chemically similar ergoloid N,N-diethyl-lysergamide (LSD), it lacks the psychedelic effects of its sister compound.