cocaine

OS-3-106 is a novel arylamide phenylpiperazines, as partial agonists at the D3R in the adenylyl cyclase inhibition assay.

Fenobam shows inverse agonist activity which blocks the mGlu5 receptor basal activity(IC50: 84 nM). Fenobam has anxiolytic activity. Fenobam is a selective and non-competitive mGluR5 antagonist acting at an allosteric modulatory site (Kd values are 54 and 31 nM for rat and human recombinant mGlu5 receptors, respectively).

Lesopitron HCl is a 5-HT1A receptor agonist with anxiolytic effects that reverses dark avoidance behavior associated with cocaine withdrawal in mice.

AMN082 is an mGluR7 agonist with antidepressant effects. AMN082 has a neuroprotective effect on neuronal apoptosis in rats with traumatic brain injury and attenuates cocaine- and morphine-induced locomotor sensitization and cross-sensitization in mice.

Opipramol (Ensidon) is a compound with antidepressant activity that attenuates cocaine-seeking behavior in a rat model of self-administration.Opipramol is a sigma (σ) receptor agonist with anxiolytic activity and may be used in the study of neurological disorders.

BP 897 is a potent and selective agonist of dopamine D3 receptor and it is a weak dopamine D2 receptor antagonist, with Kis of 0.92 nM and 61 nM for D3 and D2 receptors. Which shows low affinities at D1 and D4 receptors (Kis, 3 and 0.3 μM, respectively).

BP 897 (2-Naphthalenecarboxamide, N-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]-) is a potent and selective dopamine D3 receptor agonist, and a weak dopamine D2 receptor antagonist, with Kis of 0.92 nM and 61 nM for D3 and D2 receptors, and shows low affinities at D1 and D4 receptors (Kis, 3 and 0.3 μM, respectively).

UMB24 is an effective antagonist of the σ2 receptor, exhibiting dissociation constants (Ki values) of 170 nM for the σ2 receptor and 322 nM for the σ1 receptor. This compound mitigates cocaine-induced convulsions and hyperactivity without causing mortality.

LK-11, an alkaloid derivative, inhibits the passive uptake of norepinephrine (NA) by synaptic vesicles in the thalamus, similarly to cocaine.

Myr-Tat-CBD3 is a chemical compound that serves as an inhibitor of the protein-protein interaction between the N-type voltage-gated calcium channel Cav2.2 and collapsin response mediator protein 2 (CRMP2). This compound effectively disrupts the Cav2.2-CRMP2 interaction by about 81% at a 10 µM concentration and demonstrates an inhibitory concentration 50 (IC50) value of approximately 2.8 µM against potassium-induced calcium influx in primary rat dorsal root ganglion (DRG) neurons. Furthermore, at a concentration of 20 µM, Myr-Tat-CBD3 specifically inhibits calcium currents without affecting sodium currents in primary DRG neurons. Additionally, intrathecal administration of 20 µg/5 µl of Myr-Tat-CBD3 effectively mitigates carrageenan-induced declines in paw withdrawal latencies in rats, indicating its potential for pain relief. The compound also notably reduces cue-induced reinstatement of cocaine-seeking behavior in rats, suggesting therapeutic potential in addiction treatment.

Compound 24, a 5-HT2 agonist-1, selectively activates 5-HT2A, 5-HT2B, and 5-HT2C receptors with IC50 values of 10 nM, 8.3 nM, and 1.6 nM, respectively. The free base form of this compound is utilized in research pertaining to depression, alcoholism, tobacco and cocaine addiction, inflammation, cluster headaches, PTSD, seizure disorders, and additional CNS disorders [1].

Compound 24 (5-HT2 agonist-1 free base) is a potent agonist for 5-HT2A, 5-HT2B, and 5-HT2C receptors, exhibiting IC50 values of 10 nM, 8.3 nM, and 1.6 nM, respectively. It is utilized in research pertaining to depression, alcoholism, tobacco and cocaine addiction, inflammation, cluster headache, PTSD, seizure disorders, and other central nervous system disorders. [1]

Dopamine D3 receptor agonist 13a selectively targets the dopamine D3 receptor over dopamine D1, D2, and D4 receptors, with affinities (Ki values) of 0.14, 4,600, 2.85, and 756 nM, respectively. It also interacts with serotonin (5-HT) receptor subtypes 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C, with Ki values of 6, 54, 1.47, and 252 nM, respectively. While acting as a partial agonist at dopamine D2 receptors (EC50 = 2.26 nM in a G protein recruitment assay), it serves as an antagonist at dopamine D3 receptors (IC50 = 4.62 nM). Additionally, Dopamine D3 receptor agonist 13a, at a dose of 3 mg kg, has been shown to reduce cocaine self-administration in rats.

NGB 2904 is a potent and selective antagonist of dopamine D3 receptor (Ki values are 1.4, 217, 223, 642, > 5000, > 10000 and > 10000 nM for D3, D2, 5-HT2, α1, D4, D1 and D5 receptors respectively). NGB2904 potently antagonizes mitogenesis stimulated by quinpirole (IC50 = 6.8 nM).

AC-4-248 is an atypical, noncompetitive inhibitor of the dopamine transporter (DAT) that can reduce the inhibitory potency of cocaine on DAT. Additionally, it is a non-selective inhibitor of SLC6 transporters, with IC50 values of 45.5 μM for hDAT, 96.2 μM for hSERT, and 250 μM for hNET.

JJC8-088 dioxalate, a dioxalate salt form of JJC8-088, is a derivative of modafinil. This compound acts as an inhibitor of the dopamine transporter (DAT). In rat models, JJC8-088 dioxalate exhibits behavioral characteristics similar to those of cocaine, making it useful for research into stimulant use disorders.

MS-153, identified as a compound that activates glutamate transporters, has been shown to reduce the conditioned reward effects of morphine, methamphetamine, and cocaine, without adversely affecting the acute locomotor response in mice.

Dibutylone, a cathinone-class new psychoactive substance, exhibits notable stimulant properties. It fully substitutes for the discriminative stimulus effects of methamphetamine, cocaine, and MDMA, suggesting a similar abuse potential to these other compounds.

BD1052 is a σ-receptor agonist known to intensify the behavioral toxicity of cocaine.

RTI-51 significantly enhances locomotor activity and holds potential as a treatment compound for cocaine use. It exhibits a highly effective, selective, and long-lasting substitution effect, which can reduce drug-seeking behavior.

5-HT2A&5-HT2C agonist-1 (Example 2) is a dual-acting agent targeting 5-HT2A and 5-HT2C receptors with IC50 values of 196 nM and 0.9 nM, respectively. It is applicable in studying central nervous system disorders, including depression, alcoholism, tobacco and cocaine addiction, inflammation, cluster headaches, post-traumatic stress disorder (PTSD), and seizure disorders [1].

SCH-23390 is a dopamine D1-like receptor antagonist (with Ki values of 0.2 nM for the D1 receptor subtype and 0.3 nM for the D5 receptor subtype). It reduces the latency of lever pressing behavior induced by cocaine in rats. Additionally, SCH-23390 can eliminate generalized seizures triggered by the chemical convulsants pilocarpine and soman, making it useful for studies on neurodegenerative diseases related to the dopamine system.