RTI‐4793‐14, a new ligand with high affinity and selectivity for the (+)‐MK801‐insensitive [3H]1‐[1‐(2 thienyl)cyclohexyl]piperidine binding site (PCP site 2) of guinea pig brain

  title={RTI‐4793‐14, a new ligand with high affinity and selectivity for the (+)‐MK801‐insensitive [3H]1‐[1‐(2 thienyl)cyclohexyl]piperidine binding site (PCP site 2) of guinea pig brain},
  author={Carl B. Goodman and D. N. Thomas and Agu Pert and Betsey Emilien and Jean Lud Cadet and F. Ivy Carroll and Bruce E Blough and S Wayne Mascarella and Michael A Rogawski and Swaminathan Subramaniam and Richard B. Rothman},
[3H]TCP, an analog of the dissociative anesthetic phencyclidine (PCP), binds with high affinity to two sites in guinea pig brain membranes, one that is MK‐801 sensitive and one that is not. The MK‐801‐sensitive site (PCP site 1) is associated with NMDA receptors, whereas the MK‐801‐insensitive site (PCP site 2) may be associated with biogenic amine transporters (BAT). Although several “BAT ligands” are known that bind selectively to PCP site 2 and not to PCP site 1 (such as indatraline), these… Expand
Studies of the biogenic amine transporters. VII. Characterization of a novel cocaine binding site identified with [125I]RTI‐55 in membranes prepared from human, monkey and guinea pig caudate
Quantitative ligand binding studies revealed a novel high affinity [125I]RTI‐55 binding site assayed under 5‐HT transporter (SERT) conditions which has low affinity for almost all classic biogenic amine transporter ligands, including high affinity 5-HT transporter inhibitors such as paroxetine, but which retains high affinity for cocaine analogs. Expand
“Atypical” neuromodulatory profile of glutapyrone, a representative of a novel `class' of amino acid-containing dipeptide-mimicking 1,4-dihydropyridine (DHP) compounds: in vitro and in vivo studies
Glutapyrone displayed activity in a variety of animal models relevant for affective/depressive disorders in humans i.e. reserpine-induced ptosis and hypothermia, forced swimming test and open field test, indicating that the unusually "broad" pharmacological spectrum of glutapyr one might involve concomitant actions on multiple neurotransmitter systems, particularly, GABA-ergic and the catecholamines. Expand
An Eco-Friendly Stereoselective Synthesis of Novel Derivatives of Indeno[1,2-b]Pyrrole and Indeno[1,2-c]Pyridazine
Abstract A highly efficient and simple synthesis of a number of pharmaceutically interesting functionalized indenopirrole derivatives has been developed via the reaction of ninhydrin and acetoaceticExpand
DARK Classics in Chemical Neuroscience: Phencyclidine (PCP).
The history, importance, synthesis (both legal and clandestine), pharmacology, drug metabolism, and folklore of PCP are reviewed, a true DARK classic in chemical neuroscience. Expand
Can N-Methyl-D-Aspartate Receptor Hypofunction in Schizophrenia Be Localized to an Individual Cell Type?
A comprehensive overview detailing findings in rodent models with cell type–specific knockout of NMDARs is provided, which indicates which neuronal subtypes are particularly affected by it in terms of detrimental functional alterations. Expand


[3H]1‐[2‐(2‐thienyl)cyclohexyl]piperidine labels two high‐affinity binding sites in human cortex: Further evidence for phencyclidine binding sites associated with the biogenic amine reuptake complex
The results suggest that human cortex possesses high‐affinity PCP binding sites associated with biogenic reuptake binding sites, and that guinea pig brain, but not rat brain, may be an appropriate animal model for studying PCP site 2 in human brain. Expand
Identification of a GBR12935 homolog, LR1111, which is over 4,000‐fold selective for the dopamine transporter, relative to serotonin and norepinephrine transporters
It is demonstrated that the addition of a single methylene group in the piperazine ring results in a compound with similar affinity but significantly higher selectivity for the dopamine transporter. Expand
The psychotomimetic drug phencyclidine labels two high affinity binding sites in guinea pig brain: evidence for N-methyl-D-aspartate-coupled and dopamine reuptake carrier-associated phencyclidine binding sites.
The existence of a high affinity PCP binding site associated with the dopamine reuptake carrier is demonstrated and the possibility that the therapeutic and psychotomimetic effects of PCP in humans are separable and mediated via different binding sites is raised. Expand
[3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP): a new phencyclidine analog selective for the dopamine uptake complex.
It is demonstrated that PCP interacts with the DA uptake site since it is a competitive inhibitor of high affinity [3H]BTCP binding, however, is not the PCP receptor, which has a different pharmacological selectivity. Expand
Neurochemical Profile of Lu 19‐005, a Potent Inhibitor of Uptake of Dopamine, Noradrenaline, and Serotonin
Since DA, NA, and 5‐HT seem to be involved in depression, the profile of Lu 19–005–with equally potent activity on the three neuronal systems makes it an interesting experimental tool and a potential new antidepressant agent. Expand
Cocaine receptors labeled by [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane.
The results show that [ 3H]CFT and [3H]cocaine bind to a similar spectrum of sites in monkey caudate putamen, with a high positive correlation (r, 0.99, p less than 0.001) between the affinities of drugs at sites labeled by [3h]C FT and [4-fluorophenyl)-tropane. Expand
In vivo labelling of the mouse dopamine uptake complex with the phencyclidine derivative [3H]BTCP
Although PCP has no effect on [3H]BTCP binding in these experimental conditions, this in vivo binding model will be useful for the determination of the precise interaction of PCP and its derivatives with the striatal dopamine uptake complex in vivo independently of their interaction with the N-methyl-D-aspartate receptor-channel complex. Expand
The phencyclidine (PCP) analog N-[1-(2-benzo(B)thiophenyl) cyclohexyl]piperidine shares cocaine-like but not other characteristic behavioral effects with PCP, ketamine and MK-801.
PCP receptors, but not DA uptake mechanisms, may mediate the cocaine-like behavioral effects of PCP, ketamine and MK-801, because their order of potency in producing these effects is consistent with their potency order at PCP receptors but not at DA uptake sites. Expand
GBR12909 antagonizes the ability of cocaine to elevate extracellular levels of dopamine
The data collectively indicate that at a dose sufficient to decrease by 50% the Bmax of [3H]GBR12935 binding sites, GBR12909 antagonizes the ability of cocaine to elevate extracellular DA by 50%. Expand
1,10-Diaminodecane and 1,12-diaminododecane block NMDA receptor currents by an open channel mechanism
Results indicate that DA10 and DA12 antagonize NMDA responses via an open channel mechanism, and have been proposed to be inverse agonists at the spermine facilitatory site on the NMDA receptor. Expand