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| Formula | C24H25N3O2 |
| Molar mass | 387.483 g·mol−1 |
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Panuramine (Wy-26,002) is an antidepressant which was synthesized in 1981 by Wyeth. [1] It acts as a potent and selective serotonin reuptake inhibitor (SSRI). [2] It was never marketed. [1]
Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal or glial cell after it has performed its function of transmitting a neural impulse.
Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, obsessive–compulsive disorder (OCD), social phobia, attention-deficit hyperactivity disorder (ADHD), chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the more widely used selective serotonin reuptake inhibitors (SSRIs), which act upon serotonin only.
A norepinephrine reuptake inhibitor or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline) by blocking the action of the norepinephrine transporter (NET). This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine and therefore can increase adrenergic neurotransmission.
Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication following its continuous use of at least a month. The symptoms may include flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes, anxiety, and depression. The problem usually begins within three days and may last for several months or years. Rarely psychosis may occur.
A spontaneous orgasm, or spontaneous ejaculation when it occurs in males, is an orgasm which occurs spontaneously and involuntarily without sexual stimulation. Nocturnal emissions may be considered a normal/physiological form of spontaneous orgasm. Pathological spontaneous orgasms can be experienced as pleasurable, non-pleasurable, or unpleasant, and can be distressing. Causes of pathological spontaneous orgasms include spinal cord lesions, psychological causes, rabies, and medications. Some cases may have no identifiable cause. Spontaneous orgasms may have no trigger or may be triggered by various non-sexual circumstances. They may occur in both males and females. Treatment of spontaneous orgasms include psychotherapy, selective serotonin reuptake inhibitors (SSRIs), the alpha-1 blocker silodosin, and anxiolytics.
A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.
A reuptake inhibitor (RI) is a type of drug known as a reuptake modulator that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.
SB-242084 is a psychoactive drug and research chemical which acts as a selective antagonist for the 5HT2C receptor. It has anxiolytic effects, and enhances dopamine signalling in the limbic system, as well as having complex effects on the dopamine release produced by cocaine, increasing it in some brain regions but reducing it in others. It has been shown to increase the effectiveness of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants, and may also reduce their side effects. In animal studies, SB-242084 produced stimulant-type activity and reinforcing effects, somewhat similar to but much weaker than cocaine or amphetamines.
Talopram, also known as phthalapromine, is a selective norepinephrine reuptake inhibitor (NRI) which was researched for the management of depression in the 1960s and 1970s but was never commercialized. Along with talsupram, talopram is structurally related to the selective serotonin reuptake inhibitor (SSRI) citalopram, as well as to melitracen:
In 1971, the company hired Klaus Bøgesø as a medicinal chemist. Over the years Bøgesø turned out to have a Midas touch at the game of drug hunting, creating more molecules that made it to the market than almost any other medicinal chemist in the field. The challenge facing him in 1971 following his recruitment was to produce a selective norepinephrine reuptake inhibitor. Like other companies at the time, Lundbeck had little interest in an SSRI. Bøgesø began from an accident in the laboratory. Trying to create a derivative of their norepinephrine reuptake inhibiting antidepressant melitracen, Lundbeck chemists accidentally produced a new chemical — a phenylphthalene. Against all the odds, just like melitracen, this was also a selective norepinephrine reuptake inhibitor. Two potential antidepressants came out of this — talopram and tasulopram, which were pressed into clinical trials. Both however turned out to be energizing, and in a number of cases there were suicide attempts. The fact that there were suicide attempts appeared to confirm another proposal of Paul Kielholz, that activating antidepressants might lead to suicide. Lundbeck's experience suggested that norepinephrine reuptake inhibitors were likely to lead to just this problem. Lundbeck retreated, scared. If norepinephrine reuptake inhibitors were likely to trigger suicide, the greatest hazard of an antidepressant, then Kielholz's view suggested that an SSRI would be less likely to lead to suicide. Bøgesø's job was to see whether the new series of drugs could be converted into a series of SSRIs. Following a lead from Carlsson on how to do this, he converted talopram into citalopram, the most selective serotonin reuptake inhibitor to come to the market.
A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons.
SB-649,915 is a serotonin reuptake inhibitor and 5-HT1A and 5-HT1B receptor antagonist which is being investigated for its antidepressant effects. Relative to the selective serotonin reuptake inhibitors (SSRIs), SB-649,915 has a faster onset of action and may also have greater clinical efficacy as well. This can be attributed to blockade of 5-HT1A and 5-HT1B autoreceptors which inhibit serotonin release.
Lubazodone is an experimental antidepressant which was under development by Yamanouchi for the treatment for major depressive disorder in the late 1990s and early 2000s but was never marketed. It acts as a serotonin reuptake inhibitor and 5-HT2A receptor antagonist, and hence has the profile of a serotonin antagonist and reuptake inhibitor (SARI). The drug has good selectivity against a range of other monoamine receptors, with its next highest affinities being for the α1-adrenergic receptor and the 5-HT2C receptor. Lubazodone is structurally related to trazodone and nefazodone, but is a stronger serotonin reuptake inhibitor and weaker as a 5-HT2A receptor antagonist in comparison to them and is more balanced in its actions as a SARI. It reached phase II clinical trials for depression, but development was discontinued in 2001 reportedly due to the "erosion of the SSRI market in the United States".
Desmethylsertraline (DMS), also known as norsertraline, is an active metabolite of the antidepressant drug sertraline. Like sertraline, desmethylsertraline acts as a monoamine reuptake inhibitor, and may be responsible for some of its parent's therapeutic benefits; however, the effects of DMS's main activity of increasing serotonin levels via binding to the serotonin transporter appears to be negligible as in vivo testing showed no measurable change in brain activity despite a nearly 20-fold increase in DMS blood levels compared to the EC50 (i.e. the amount required to achieve the desired effect in 50% of the population) of its parent drug sertraline. DMS is significantly less potent relative to sertraline as a serotonin reuptake inhibitor (Ki = 76 nM vs. 3 nM, respectively), but conversely, is more balanced as a monoamine reuptake inhibitor (5-HT (Ki) = 76 nM; NE (Ki) = 420 nM; DA (Ki) = 440 nM), which has the effective result of DMS contrarily behaving as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI), with about 5.5-fold preference for inhibiting serotonin reuptake relative to catecholamine reuptake.
JZ-IV-10 is a piperidine derivative related to cocaine which acts as a highly potent serotonin–norepinephrine–dopamine reuptake inhibitor. The eugeroic modafinil was used as a lead to fuel this compound's discovery.
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
Ifoxetine (CGP-15,210-G) is a selective serotonin reuptake inhibitor (SSRI) which was investigated as an antidepressant in the 1980s but was never marketed. Ifoxetine selectively blocks the reuptake of serotonin in the brain supposedly without affecting it in the periphery. Supporting this claim, ifoxetine was found to be efficacious in clinical trials and was very well tolerated, producing almost no physical side effects or other complaints of significant concern.
A serotonin–dopamine reuptake inhibitor (SDRI) is a type of drug which acts as a reuptake inhibitor of the monoamine neurotransmitters serotonin and dopamine by blocking the actions of the serotonin transporter (SERT) and dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of serotonin and dopamine, and, therefore, an increase in serotonergic and dopaminergic neurotransmission.
A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.
A serotonin modulator and stimulator (SMS), sometimes referred to more simply as a serotonin modulator, is a type of drug with a multimodal action specific to the serotonin neurotransmitter system. To be precise, SMSs simultaneously modulate one or more serotonin receptors and inhibit the reuptake of serotonin. The term was created to describe the mechanism of action of the serotonergic antidepressant vortioxetine, which acts as a serotonin reuptake inhibitor (SRI), agonist of the 5-HT1A receptor, and antagonist of the 5-HT3 and 5-HT7 receptors. However, it can also technically be applied to vilazodone, which is an antidepressant as well and acts as an SRI and 5-HT1A receptor partial agonist.
