British Journal of Pharmacology
January 1, 2015
B Simonson, A S Morani, A W M Ewald et al.
A synthetic version of salvinorin A, Mesyl Sal B, activates κ opioid receptors and shows potential as an anticocaine agent with fewer adverse effects than classic κ agonists. In rats, Mesyl Sal B had a longer duration of action than salvinorin A, reduced cocaine-seeking behavior, and increased dopamine transporter function in vitro through a κ opioid receptor- and ERK1/2-dependent mechanism. Unlike salvinorin A, Mesyl Sal B raised the maximum rate of dopamine uptake without increasing transporter cell-surface expression. The findings suggest that salvinorin-based compounds like Mesyl Sal B warrant further study as treatments for cocaine addiction, though their side-effect profile requires additional investigation.
British Journal of Pharmacology
June 1, 2002
Claudio Acuña-Castillo, Claudio A Villalobos, Pablo R Moya et al.
A series of phenylisopropylamines and phenylethylamines were tested on rat serotonin 5-HT2A and 5-HT2C receptors expressed in frog eggs. All compounds acted as full agonists at 5-HT2C receptors, while at 5-HT2A receptors they were partial agonists, with relative efficacy ranging from 22% to 58% of serotonin's effect. The phenylethylamines had lower or undetectable efficacy at 5-HT2A receptors. DOI was a full agonist at 5-HT2C, while 2C-N acted as an antagonist at both receptors, competitive at 5-HT2A but non-competitive at 5-HT2C. The alpha-methyl group on the drugs determined their efficacy at both receptor subtypes.
British Journal of Pharmacology
July 1, 2000
M Bujas-Bobanovic, D C Bird, H A Robertson et al.
In rats, the drug phencyclidine (PCP) produced a complex behavioral syndrome including hyperlocomotion, stereotyped behaviors, and ataxia, and increased expression of the neuronal activity marker c-fos in brain regions, especially the cortex. The nitric oxide donor sodium nitroprusside (SNP) alone had no effect but completely blocked both the behavioral and c-fos responses to PCP in a dose- and time-dependent manner. These findings implicate the nitric oxide system in PCP's mechanism and suggest that drugs targeting the glutamate-nitric oxide system could offer a novel treatment approach for PCP-induced psychosis and schizophrenia.
British Journal of Pharmacology
September 1, 1999
D T Malone, D A Taylor
Delta9-tetrahydrocannabinol (THC) increased dopamine release in the striatum of conscious, freely-moving rats in a dose-dependent manner, with maximum increases of 42% to 97% above baseline occurring 20 minutes after intravenous administration. This effect was blocked by a cannabinoid CB1 receptor antagonist and by pretreatment with the antidepressant fluoxetine. However, fluoxetine administered after THC or perfused locally into the striatum potentiated the dopamine release. The authors suggest that THC-induced dopamine release is modulated by serotoninergic changes, with fluoxetine's effect depending on timing of administration.
British Journal of Pharmacology
August 1, 1990
L I Backus, T Sharp, D G Grahame-Smith
Blocking 5-HT2 receptors with antagonists such as ritanserin, ICI 170,809, or low-dose ketanserin enhances the behavioral syndrome caused by 5-HT1A receptor activation in rats, suggesting that 5-HT2 receptors normally inhibit 5-HT1A-mediated responses. Higher doses of ketanserin reduce the syndrome, likely due to additional alpha1-adrenoceptor blockade. The enhancement is not due to general behavioral activation, as the antagonists do not affect apomorphine-induced stereotypy or hyperactivity. These findings indicate a regulatory interaction between 5-HT2 and 5-HT1A receptor systems.