Gianluigi Tanda

• Pharmacy Doctor & Toxicology Specialization (PhD)
• Staff Scientist; Deputy Director of the Medication Develpment Program at National Institute on Drug Abuse/IRP NIH; Baltimore

Psychostimulant use disorders (PSUD) are prevalent; however, no FDA‐approved medications have been made available for treatment. Previous studies have shown that dual inhibitors of the dopamine transporter (DAT) and sigma receptors significantly reduce the behavioral/reinforcing effects of cocaine, which have been associated with stimulation of ext...

Understanding the neurochemistry underlying sex differences in psychostimulant use disorders (PSUD) is essential for developing related therapeutics. Many psychostimulants, like cocaine, inhibit the dopamine transporter (DAT), which is largely thought to account for actions related to their misuse and dependence. Cocaine-like, typical DAT inhibitor...

Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there are some sex differences in the onset of dependence, relapse rates, and treatment success with PSUD observed in preclinical and clinical studies. The subtle sex differences observed...

Typical and atypical dopamine uptake inhibitors (DUIs) prefer distinct conformations of the dopamine transporter (DAT) to form ligand-transporter complexes, resulting in markedly different effects on behavior, neurochemistry, and potential for addiction. Here we show that cocaine and cocaine-like typical psychostimulants elicit changes in DA dynami...

While the illicit use and misuse of stimulants like cocaine and methylphenidate (MP) has increased, there remains no FDA‐approved treatments for psychostimulant use disorders (PSUD). Oxytocin (OT) has shown promise as a potential pharmacotherapy for PSUD. Dopamine (DA) neurotransmission plays a significant role in PSUD. We have recently shown that...

Cocaine binds to the dopamine (DA) transporter (DAT) to regulate cocaine reward and seeking behavior. Zinc (Zn2+) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that Zn2+ concentrations in postmortem brain (caudate) tissue from humans who died of cocaine overdose were significantly lower than in control su...

Despite the high prevalence of obesity, little is known about its potential impact on the pharmacokinetics of psychotropic drugs. In the course of investigating the role of the microRNA system on neuronal signaling, we found that mice lacking the translin/trax microRNA-degrading enzyme display an exaggerated locomotor response to amphetamine. As th...

The number of individuals affected by psychostimulant use disorder (PSUD) has increased rapidly over the last few decades resulting in economic, emotional, and physical burdens on our society. Further compounding this issue is the current lack of clinically approved medications to treat this disorder. The dopamine transporter (DAT) is a common targ...

Cocaine exerts its stimulant effect by inhibiting dopamine reuptake leading to increased dopamine signaling. This action is thought to reflect binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share the behavioral actions of cocaine. W...

The translin/trax microRNA-degrading enzyme mediates activity-induced changes in translation that underlie several long-lasting forms of cellular plasticity. As translin and trax are expressed in dopaminergic and striatal neurons, we investigated whether deletion of Tsn blocks amphetamine sensitization, a long-lasting, translation-dependent form of...

Pharmacotherapeutics for treatment of psychostimulant use disorder are still an unmet medical goal. Recently, off label use of modafinil (MOD), an approved medication for treatment of sleep disturbances, has been tested as a therapeutic for cocaine and methamphetamine use disorder. Positive results have been found in subjects dependent on psychosti...

Cocaine binds to the dopamine transporter (DAT) in the striatum to regulate cocaine reward and seeking behavior. Zinc (Zn ²⁺ ) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that cocaine abuse in humans correlated with low postmortem striatal Zn ²⁺ content. In mice, cocaine decreased striatal vesicular Zn...

Despite considerable efforts to develop medications to treat psychostimulant use disorders, none have proven effective, leaving an underserved patient population and unanswered questions as to what mechanism(s) of action should be targeted for developing pharmacotherapies. Atypical dopamine transporter (DAT) inhibitors, based on (±)modafinil, have...

Modafinil and methylphenidate are among the few clinically available medications that block the dopamine (DA) transporter (DAT), a mechanism shared by abused psychostimulants like cocaine. Modafinil is FDA approved for the treatment of narcolepsy and other sleep disorders, while methylphenidate is approved as a medication for neurological disorders...

Cocaine exerts its stimulant effect by inhibiting dopamine reuptake leading to increased dopamine signaling. This action is thought to reflect binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share the behavioral actions of cocaine. H...

Modafinil and methylphenidate are medications that inhibit the neuronal reuptake of dopamine, a mechanism shared with cocaine. Their use as “smart drugs” by healthy subjects poses health concerns and requires investigation. We show that methylphenidate, but not modafinil, maintained intravenous self-administration in Sprague-Dawley rats similar to...

Atypical dopamine transporter (DAT) inhibitors have shown therapeutic potential in preclinical models of psychostimulant abuse. In rats, 1-(4-(2-((bis(4-fluorophenyl)methyl)sulfinyl)ethyl)-piperazin-1-yl)-propan-2-ol (3b) was effective in reducing the reinforcing effects of both cocaine and methamphetamine, but did not exhibit psychostimulant behav...

The neuropeptide oxytocin (OT) alters behaviors related to the administration of drugs of abuse, including stimulants. OT also plays a key role in social bonding, which involves an interaction between OT and dopamine (DA) in the nucleus accumbens (NAc). The nature of the interaction between OT and DA in the striatum in the context of psychostimulan...

The reinforcing effects of Δ9-tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynurenic acid (KYNA) through systemic administration of the kynurenine 3-monooxygenase inhibitor, Ro 61-8048. KYNA is a negative allosteric modul...

Modafinil has been used off‐label to treat psychostimulant use disorders (PSUD). However, its effectiveness in clinical trials seems limited to a subpopulation of subjects without concurrent alcohol or poly‐drug use. Since the main pharmacological target of cocaine is the dopamine transporter (DAT), recent efforts to develop more globally effective...

Dopamine uptake inhibitors (DUIs), such as cocaine and methylphenidate, are characterized by their ability to bind to the dopamine transporter (DAT) and prevent dopamine (DA) from being transported from the extracellular to the intracellular side of a neuronal terminal. It was originally posited that all DUIs would have the same effect on behavior,...

Medication-assisted treatments are unavailable to patients with cocaine use disorders. Efforts to develop potential pharmacotherapies have led to the identification of a promising lead molecule, JJC8-091, that demonstrates a novel binding mode at the dopamine transporter (DAT). Here, JJC8-091 and a structural analogue, JJC8-088, were extensively an...

The Toll-like receptor 4 (TLR4) antagonists, (+)-naloxone and (+)-naltrexone, have been reported to decrease self-administration of opioids in rats and to reduce other preclinical indicators of abuse potential. However, under the self-administration conditions studied, the effects of TLR4 antagonists were not reinforcer selective, questioning the i...

Recent discoveries have improved our understanding of the physiological and pathological roles of the dopamine transporter (DAT); however, only a few drugs are clinically available for DAT-implicated disorders. Among those drugs, modafinil (MOD) and its (R)-enantiomer (R-MOD) have been used off-label as therapies for psychostimulant use disorders,...

Psychostimulant use disorders remain an unabated public health concern worldwide, but no FDA approved medications are currently available for treatment. Modafinil (MOD), like cocaine is a dopamine reuptake inhibitor, and one of the few drugs evaluated in clinical trials that has shown promise for the treatment of cocaine or methamphetamine use diso...

Atypical dopamine uptake inhibitors (DUIs) bind to the dopamine transporter and inhibit the reuptake of dopamine but have lower abuse potential than psychostimulants. Several atypical DUIs can block abuse-related effects of cocaine and methamphetamine, thus making them potential medication candidates for psychostimulant use disorders. The aim of th...

Clinical and preclinical reports have shown that the hypothalamic neurohormone oxytocin plays a role in social bonding, a behavior that is also controlled by the neurotransmitter dopamine. Dopamine also plays an important role in both natural and pathologic behaviors related to reward and reinforcement, including substance use disorders. Dopamine i...

Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant phytocannabinoids found in can...

Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa. Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain...

Abstract: Opioid addiction, including misuse of prescription pain relievers and abuse of illicit substances, is an exploding national crisis. It is estimated that greater than 2 million individuals suffer from the effects of substance abuse and withdrawal cycles nationwide. Prolonged usage of opioids produces cellular and molecular neuroadaptations...

Introduction Dopamine (DA) transmission in mesolimbic areas is intimately involved in the mediation of natural‐ and drug‐reinforcing behavioral effects. However, oxytocin has been shown to interfere with psychostimulant‐induced behavioral effects, the mechanism for which is unknown. We have recently shown that systemic, peripheral oxytocin (10 min...

Atypical dopamine uptake inhibitors (DUIs), such as JHW 007, bind to the dopamine transporter (DAT), the same pharmacological target shared by psychostimulants such as cocaine and methamphetamine. Atypical DUIs show lower efficacy compared to typical ones in eliciting motor activation or producing the rewarding/reinforcing effects that might lead t...

There is renewed interest in using electroencephalogram (EEG) as a tool to improve early diagnosis of neurological and behavioral disorders and to assist the preclinical development of related pharmacotherapies. Atypical dopamine uptake inhibitors (DUIs) bind with nano to micromolar affinities to the dopamine transporter and produce some of the eff...

The neuropeptide oxytocin plays a role in social bonding as well as learning and memory. Rodent studies have investigated whether oxytocin can reverse the neuroadaptations that occur with repeated cocaine and psychostimulant use. There is increasing evidence that oxytocin’s effects on these processes are centrally mediated and that these effects ar...

Methamphetamine (METH) is a highly addictive drug, but no pharmacological treatment is yet available for METH use disorders. Similar to METH, the wake-promoting drug (R)-modafinil (R-MOD) binds to the dopamine transporter (DAT). Unlike METH, R-MOD is not a substrate for transport by DAT and has low abuse potential. We tested the hypothesis that the...

(±)Modafinil ((±)MOD) and its R-enantiomer (R-modafinil; R-MOD) have been investigated for their potential as treatments for psychostimulant addiction. We recently reported a series of (±)MOD analogues, of which JJC8-016 (N-(2-((bis(4-fluorophenyl)methyl)thio)ethyl)-3-phenylpropan-1-amine) was selected for further development. JJC8-016 and R-MOD we...

Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performe...

Effective medications for drug abuse remain a largely unmet goal in biomedical science. Recently, the (+)-enantiomers of naloxone and naltrexone, TLR4 antagonists, have been reported to attenuate preclinical indicators of both opioid and stimulant abuse. To further examine the potential of these compounds as drug-abuse treatments we extended the pr...

Rationale: The reinforcing effects of most abused drugs have been consistently demonstrated and studied in animal models, although those of marijuana were not, until the demonstration 15 years ago that delta-9-tetrahydrocannabinol (THC) could serve as a reinforcer in self-administration (SA) procedures in squirrel monkeys. Until then, those effect...

The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning, and memory processes. As such, there is increasing interest in oxytocin as a potential treatment for addictions. The endogenous oxytocin system is itself altered by short- or long-term exposure to drugs of abuse. A large number of preclinical studies in rodents...

Modafinil (MOD) and methylphenidate (MPH) are FDA‐approved wakefulness‐promoting agents, and MPH is also approved as a medication to treat attention deficit disorders. College students, who misuse MOD and MPH as “smart drugs” to increase cognitive performance, are also likely a population at high risk for abuse of illicit stimulants, such as cocain...

Background Subjective effects related to cocaine abuse are primarily mediated by blockade of the dopamine (DA) transporter (DAT). The present study assessed the hypothesis that different conformational equilibria of the DAT regulate differences in extracellular DA induced by structurally diverse DA uptake inhibitors (DUI) and their cocaine-like sub...

Rationale: The only systematic in vivo studies comparing antipsychotic (AP) effects on nucleus accumbens (NAc) shell and core dopamine (DA) transmission are voltammetric studies performed in pargyline-pretreated, halothane-anaesthetized rats. Studies in freely moving rats not pretreated with pargyline are not available. This study was intended to...

Yohimbine is an alpha-2 adrenoceptor antagonist that has been used in numerous studies as a pharmacological stressor in rodents, monkeys and humans. Recently, yohimbine has become the most common stress manipulation in studies on reinstatement of drug and food seeking. However, the wide range of conditions under which yohimbine promotes reward seek...

A continuing challenge in treating depression is therapeutic delay and resistance to available treatments. Hence, the growing interest in developing antidepressants (AD) with rapid onset (hours to days) and novel mechanisms of action. For example, the glutamatergic antagonist ketamine has rapid AD efficacy but is limited by poor bioavailability, sh...

Atypical dopamine-uptake inhibitors have low abuse potential and may serve as leads for development of cocaine-abuse treatments. Among them, the benztropine (BZT) derivatives, N-butyl (JHW007), N-allyl (AHN2-005), and N-methyl (AHN1-055) analogs of 3α-[bis(4'-fluorophenyl)methoxy]-tropane dose-dependently decreased cocaine self-administration witho...

In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increase...

Modafinil (MOD) and its R-enantiomer (R-MOD) are approved medications for narcolepsy and other sleep disorders. They have also been used, off-label, as cognitive enhancers in populations of patients with mental disorders, including substance abusers that demonstrate impaired cognitive function. A debated nonmedical use of MOD in healthy individuals...

The endocannabinoid system has been implicated in the development of synaptic plasticity induced by several drugs abused by humans, including cocaine. However, there remains some debate about the involvement of cannabinoid receptors/ligands in cocaine-induced plasticity and corresponding behavioral actions. Here, we show that a single cocaine injec...

A previous study showed that cocaine self-administration induced dopamine-independent reinforcing effects of selective agonists mediated by their actions at sigma1 receptors (σ1Rs), which are intracellularly-mobile chaperone proteins implicated in abuse-related effects of stimulants. The present study assessed whether the induction was specific to...

Rationale The rewarding effects of alcohol have been attributed to interactions between opioid and dopaminergic system within the mesolimbic reward pathway. We have previously shown that ablation of β-arrestin 2 (Arrb2), a crucial regulator of μ-opioid receptor function, attenuates alcohol-induced hyperlocomotion and c-fos activation in the nucleus...

Rationale: Dopamine transporter (DAT) conformation plays a role in the effectiveness of cocaine-like and other DAT inhibitors. Cocaine-like stimulants are intolerant to DAT conformation changes having decreased potency in cells transfected with DAT constructs that face the cytosol compared to wild-type DAT. In contrast, analogs of benztropine (BZT...

Sigma1 receptors (σ 1 Rs) are intracellularly‐mobile chaperone proteins implicated in several diseases, as well as psychiatric disorders and substance abuse. A previous study showed that cocaine self‐administration (SA) induced dopamine (DA)‐independent reinforcing effects of selective σ 1 R agonists. The present study assessed whether the inductio...

Previous studies indicate that benztropine (BZT) analogs bind to the dopamine transporter (DAT), inhibit DA uptake, are less effective than cocaine in a variety of procedures, and block cocaine self administration. Previously studied BZT analogs have a low apparent rate of association, which has been hypothesized to contribute to their lower cocain...

Recent research with animal models of human drug dependence has demonstrated that a receptor related to the endogenous cannabinoid system, the peroxisome proliferator-activated alpha nuclear receptor (PPARα), which regulates genes involved in lipid metabolism and inflammatory responses, is a viable target for treating nicotine dependence. The endog...

Sigma(1) receptors (σ(1)Rs) are intracellularly mobile chaperone proteins implicated in several disease processes, as well as psychiatric disorders and substance abuse. Here we report that although selective σ(1)R agonists (PRE-084, (+)-pentazocine) lacked reinforcing effects in drug-naive rats, over the course of 28 experimental sessions, which wa...

(±)-Modafinil has piqued interest as a treatment for attention-deficit/hyperactivity disorder and stimulant dependence. The R-enantiomer of modafinil might have unique pharmacological properties that should be further investigated. (±)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of [(3)H] dopamine (DA)...

Rimcazole (RIM) is a sigma receptor (σR) antagonist that also has affinity for the dopamine (DA) transporter (DAT). Despite this DAT affinity, RIM lacks stimulant effects and dose‐dependently attenuates ambulatory effects of cocaine (COC). RIM and its analogs decrease COC self‐administration in rats (JPET 339: 662), an effect that is obtained neith...

Sigma1 receptors (σ1Rs) represent a structurally unique class of intracellular proteins that function as chaperones. σ1Rs translocate from the mitochondria-associated membrane to the cell nucleus or cell membrane, and through protein-protein interactions influence several targets, including ion channels, G-protein-coupled receptors, lipids, and oth...

Previous studies demonstrated the effectiveness of selective σ-receptor (σR) agonists [1,3-di-o-tolylguanidine (DTG), PRE-084] as reinforcers in rats trained to self-administer cocaine. Similar to cocaine, these drugs increased nucleus accumbens shell dopamine levels, and effects of DTG, but not PRE-084, on dopamine seemed to be mediated by σRs. In...

Sigma receptor (σR) antagonists attenuate many behavioral effects of cocaine but typically not its reinforcing effects in self-administration procedures. However, the σR antagonist rimcazole and its N-propylphenyl analogs, [3-(cis-3,5-dimethyl-4-[3-phenylpropyl]-1-piperazinyl)-propyl]diphenylamine hydrochloride (SH 3-24) and 9-[3-(cis-3,5-dimethyl-...

Recent findings indicate that inhibitors of fatty acid amide hydrolase (FAAH) counteract the rewarding effects of nicotine in rats. Inhibition of FAAH increases levels of several endogenous substances in the brain, including the endocannabinoid anandamide and the noncannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanola...

Subtypes of sigma (σ) receptors, σ₁ and σ₂, can be pharmacologically distinguished, and each may be involved in substance-abuse disorders. σ-Receptor antagonists block cocaine place conditioning and σ-receptor agonists are self-administered in rats that previously self-administered cocaine. Self-administration of abused drugs has been related to in...

Although delta-9-tetreahydrocannabinol (THC)-induced elevations in accumbal dopamine levels are believed to play an important role in the abuse-related effects of cannabis, little direct evidence has been provided that the dopaminergic system is involved in the psychotropic effects of THC. The objective of this study is to investigate whether drugs...

Stimulant drugs acting at the dopamine transporter (DAT), like cocaine, are widely abused, yet effective medical treatments for this abuse have not been found. Analogs of benztropine (BZT) that, like cocaine, act at the DAT have effects that differ from cocaine and in some situations block the behavioral, neurochemical, and reinforcing actions of c...

sigma-Receptor (sigmaR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of sigmaR ligands in rats trained to self-administer cocaine (0.032-1.0 mg/kg/inj i.v.) under fixed-ratio 5-response schedules of reinforcement. Maximal rates of responding were maintained by 0.32 mg/kg/in...

Drugs that inhibit dopamine (DA) reuptake through actions at the dopamine transporter (DAT) have been proposed as candidates for development as pharmacotherapies for cocaine abuse. Accordingly, it is important to understand the potential pharmacological interactions of cocaine with other drugs acting at the DAT. Effects of combinations of cocaine w...

Sigma receptors (σRs) can modulate cocaine's behavioral effects, which are related to increased mesolimbic dopamine (DA) neurotransmission, and σR agonists can maintain responding in rats that self administer cocaine. We report here effects of σR ligands on DA transmission in rats implanted with vertical microdialysis probes in the nucleus accumben...

Prior results suggest that rimcazole and its analogues decrease cocaine self administration (SA) through actions mediated by antagonist effects at sigma 1 receptors (σ 1 Rs) along with blockade of the dopamine transporter (DAT). The present study compared several analogues of rimcazole for the optimum ratio of σ 1 R to DAT affinity for effects on c...

Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB(1)-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain. Using a passive...

Cannabinoids are usually abused by humans in the form of marijuana. They are the most frequently abused illicit class of drugs in the United States, but no pharmacological treatment is currently available to help in reducing marijuana abuse and dependence. Although the dopaminergic system plays a critical role in the reinforcing effects of drugs of...

Tobacco addiction is one of the leading preventable causes of mortality in the world and nicotine appears to be the main critical psychoactive component in establishing and maintaining tobacco dependence. Several lines of evidence suggest that the rewarding effects of nicotine, which underlie its abuse potential, can be modulated by manipulating th...

Emerging evidence suggests that the rewarding, abuse-related effects of nicotine are modulated by the endocannabinoid system of the brain. For example, pharmacological blockade or genetic deletion of cannabinoid CB(1) receptors can reduce or eliminate many abuse-related behavioral and neurochemical effects of nicotine. Furthermore, doses of Delta(9...

The pattern of activation of dopamine (DA) neurotransmission in the nucleus accumbens (NAc) of rats produced by H(1) histamine antagonists which have behavioral effects like those of psychostimulant drugs was examined. Diphenhydramine and (+)-chlorpheniramine were compared with triprolidine, a potent and selective H(1) antagonist and (-)-chlorpheni...

Accumulating evidence suggests the endocannabinoid system modulates environmental cues' ability to induce seeking of drugs, including nicotine and alcohol. However, little attention has been directed toward extending these advances to the growing problem of cannabis use disorders. Therefore, we studied intravenous self-administration of Delta(9)-te...

Worldwide more than 3 million deaths a year are attributable to smoking, and tobacco use is on the rise in developing countries. Consequently, smoking is one of the few causes of mortality that is increasing, with deaths projected to reach 10 million annually in 30-40 years. Cannabinoids, which are usually used in the form of marijuana, have become...

Converging evidence suggests that the endocannabinoid system is an important constituent of neuronal substrates involved in brain reward processes and emotional responses to stress. Here, we evaluated motivational effects of intravenously administered anandamide, an endogenous ligand for cannabinoid CB1-receptors, in Sprague-Dawley rats, using a pl...

Human immunodeficiency virus type 1 (HIV-1) causes neuronal degeneration and, at a late stage, creates HIV-associated dementia (HAD) and other neurological abnormalities. Therefore, the need for neuroprotective agents is great. However, therapeutic agents that reduce HIV neurotoxicity are difficult to characterize and develop because rodents are no...

Dependence on cocaine is still a main unresolved medical and social concern, and in spite of research efforts, no pharmacological therapy against cocaine dependence is yet available. Recent studies have shown that the endocannabinoid system participates in specific stages and aspects of drug dependence in general, and some of this evidence suggests...

Previous studies of benztropine analogues have found them to inhibit dopamine uptake like cocaine, but with less effectiveness than cocaine in producing behavioral effects related to drug abuse. Studies have assessed whether nonselective muscarinic antagonists decrease the effects of cocaine because many of the benztropine analogues are also muscar...

Progressive and irreversible loss of specific neuronal cell populations is commonly seen in chronic neurodegenerative diseases such as Parkinson's disease (PD). Evidence is accumulating that apoptosis is a crucial cellular event responsible for the dysfunction and death of neurons in this disease. Thus, limiting apoptosis may prevent disease pathog...

Systemic administration of the main active ingredient in cannabis, Delta9-tetrahydrocannabinol (THC), alters extracellular levels of acetylcholine in several brain areas, suggesting an involvement of the cholinergic system in the psychotropic effects of cannabis. Here, we investigated whether drugs acting at either nicotinic or muscarinic receptors...