Pharmacology, biochemistry, and behavior
January 1, 2006
W E Fantegrossi, A W Harrington, C L Kiessel et al.
144 citations
5-MeO-DIPT, a hallucinogenic drug similar to DMT, produced head-twitch responses in mice, an effect blocked by a serotonin 2A receptor antagonist. In rats trained to recognize LSD, 5-MeO-DIPT partially substituted for LSD (75% generalization) and suppressed response rates in a dose-dependent way; this effect was abolished by a 5-HT2A antagonist but not by a 5-HT1A antagonist. The drug showed micromolar affinity for 5-HT2A and 5-HT2C receptors and much higher affinity for 5-HT1A receptors in rat brain tissue. The results indicate that the 5-HT2A receptor is a key site of action for 5-MeO-DIPT, despite its in vitro selectivity for the 5-HT1A receptor.
Psychopharmacology
September 1, 1996
J K Staley, Q Ouyang, J Pablo et al.
82 citations
Ibogaine, a treatment for drug dependence, is metabolized into 12-hydroxyibogamine (12-OH ibogamine). Both the parent drug and metabolite bind to similar molecular targets, with the highest potency at the cocaine recognition site on the serotonin transporter. The metabolite shows higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor compared to ibogaine. Micromolar concentrations of both compounds are found in rat brain. The combined actions of ibogaine and its metabolite at key pharmacological targets may alter drug-seeking behavior by modulating reward circuits.
Pharmacology, biochemistry, and behavior
October 1, 2007
J C Winter, K C Rice, D J Amorosi et al.
73 citations
Psilocybin produces a complex internal cue in rats that depends partly, but not entirely, on the 5-HT2A serotonin receptor. Blocking the 5-HT2A receptor with M100907 only partially reduced the drug's effect, while blocking the 5-HT1A/7 receptor or the dopamine D2 receptor had no effect. Rats trained to recognize psilocybin also recognized other hallucinogens such as LSD, psilocin, and DOM, and partially recognized mescaline and 2C-T-7. LSD and MDMA partly substituted for psilocybin, and those effects were fully blocked by M100907. Unlike the related hallucinogen 5-MeO-DMT, psilocybin's effects do not involve the 5-HT1A receptor.
Synapse (New York, N.Y.)
August 1, 1991
H C Akunne, A A Reid, A Thurkauf et al.
The brain contains two types of PCP binding sites: site 1 (linked to the NMDA receptor) and site 2 (linked to the dopamine reuptake complex). This work examined brain membranes from multiple species and found detectable site 2 in guinea pig, rabbit, pig, mouse, sheep, and human, but not in rat or chicken. In human cortex, site 2 was the predominant binding site. Dopamine and serotonin uptake inhibitors produced a wash-resistant inhibition of [3H]TCP binding to site 2 but not site 1. The results suggest human cortex possesses high-affinity PCP binding sites associated with biogenic reuptake binding sites, and that guinea pig, but not rat, may be an appropriate animal model for studying PCP site 2 in human brain.
Neuropharmacology
September 1, 1990
A A Reid, M V Mattson, B R De Costa et al.
Phencyclidine (PCP) and its analog TCP bind non-selectively to two high-affinity binding sites in guinea pig brain: one coupled to the NMDA glutamate receptor (site 1) and the other associated with the dopamine reuptake carrier (site 2). The compound (+)MK801 is highly selective for site 1 and produces minimal psychotomimetic effects in humans at doses that reduce seizures, whereas PCP produces psychotomimetic effects. This suggests that (+)MK801 can serve as a marker for site 1 and that PCP's psychotomimetic effects may be mediated by site 2.