Psychiatric Drugs - Educational thread

[Petros Agapetos]

Trintellix is an atypical antidepressant, a serotonin modulator and stimulator.

Pharmacodynamics
Trintelix is a so-called "serotonin modulator and stimulator". It has been shown to possess the following pharmacological actions:

SERT*[Serotonin transporter] Inhibition
NET*[Norepinephrine transporter] Inhibition
5-HT1A*Agonist
5-HT1B* Partial agonist
5-HT1D*Antagonist
5-HT3*Antagonist
5-HT7*Antagonist

Note: 5HT stands for serotonin; the above are serotonin receptors that Trintelix targets in the brain. An increase in serotonin receptor activity is associated with relief of depressive symptoms.

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 Trintellix, which acts as a serotonin reuptake inhibitor (SRI), partial agonist of the 5-HT1A receptor, and antagonist of the 5-HT3 and 5-HT7 receptors.

SMSs were developed because there are many different subtypes of serotonin receptors (at least 15 in total are currently known) and not all of these receptors appear to be involved in the antidepressant effects of SRIs. Some serotonin receptors seem to play a relatively neutral or insignificant role in the regulation of mood, but others, such as 5-HT1A autoreceptors and 5-HT7 receptors, appear to play an oppositional role in the efficacy of SRIs in treating depression. As such, a drug which combines the actions of, say, an SRI, 5-HT1A partial agonism, and 5-HT7 receptor antagonism, could, in theory, have the potential to prove more effective than pure SRIs.

An alternative term is serotonin partial agonist/reuptake inhibitor (SPARI).

[Petros Agapetos]

Abilify (Aripriprazole) is a partial agonist on the dopamine D2, D3, and D4 receptors, and an antagonist at D1 and D5. Abilify is also a 5HT1A partial agonist and a 5HT2A antagonist. Abilify is an effective add-on treatment for major depressive disorder.


Binding profile

Abilify acts as an antagonist/inverse agonist (unless otherwise noted) of the following receptors and transporters:

Receptor Ki (nM)
5-HT1A 5.6 Partial agonism
5-HT1B 832
5-HT1D 65.5
5-HT2A 8.7
5-HT2B 0.4
5-HT2C 22.4 Partial agonism
5-HT3 628
5-HT5A 1240
5-HT6 642
5-HT7 10 Weak partial agonism /antagonism
D1 1170
D2 1.6 Partial agonism
D3 5.4 Partial agonism
D4 514 Partial agonism
D5 2130
α1A 25.9
α1B 34.4
α2A 74.1
α2B 102
α2C 37.6
β1 141
β2 163
H1 27.9
M1 6780
M2 3510
M3 4680
M4 1520
M5 2330
SERT 1080
NET 2090
DAT 3220

Abilify's mechanism of action is different from those of the other FDA-approved atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, ziprasidone, and risperidone). Rather than antagonizing the D2 receptor, aripiprazole acts as a D2 partial agonist. Aripiprazole is also a partial agonist at the 5-HT1A receptor, and like the other atypical antipsychotics displays an antagonist profile at the 5-HT2A receptor. It also antagonizes the 5-HT7 receptor and acts as a partial agonist at the 5-HT2C receptor, both with high affinity. The latter action may underlie the minimal weight gain seen in the course of therapy. Abilify has moderate affinity for histamine, α-adrenergic, and D4 receptors as well as the serotonin transporter, while it has no appreciable affinity for cholinergic muscarinic receptors.

D2 and D3 receptor occupancy levels are high, with average levels ranging between ~71% at 2 mg/day to ~96% at 40 mg/day. Most atypical antipsychotics bind preferentially to extrastriatal receptors, but aripiprazole appears to be less preferential in this regard, as binding rates are high throughout the brain.

Abilify acts by modulating neurotransmission overactivity on the dopaminergic mesolimbic pathway, which is thought to be the cause of positive schizophrenia symptoms. Due to its agonist activity on D2 receptors, aripiprazole may also increase dopaminergic activity to optimal levels in the mesocortical pathways where it is reduced.

[Petros Agapetos]

If you have questions about these antidepressants, please don't hesitate to ask. I'll do my best to assist you with information.

[Petros Agapetos]

Bupropion is a dopamine and norepinephrine reuptake inhibitor, an antidepressant. It is known to affect several different biological targets. It often is described as a norepinephrine-dopamine reuptake inhibitor (NDRI), and is also a nicotinic antagonist. Based on preclinical research with animal and human proteins, bupropion has been characterized as a weak norepinephrine-dopamine reuptake inhibitor (NDRI). It has also been found to act as a releasing agent of dopamine and norepinephrine (NDRA), similarly to other cathinones. However, when ingested orally by humans, bupropion is extensively converted in the body into several active metabolites with differing activities and influences on the effects of the drug during first-pass metabolism. These metabolites are present in much higher concentrations in the body compared to bupropion itself. The most important example is the major metabolite of bupropion, hydroxybupropion, a selective norepinephrine reuptake inhibitor (and likely releasing agent) and nicotinic acetylcholine receptor (nAChR) antagonist that lacks significant dopaminergic actions, and which, with oral bupropion treatment, can reach area under the curve (AUC) plasma concentrations that are as much as 16–20 times greater than those of bupropion itself. Hence, the effects of bupropion cannot be understood unless its metabolism is also considered.

Buproprion works by increasing the intrasynaptic dopamine and norepinephrine content allowing more of these chemical messengers to be present at target receptor sites, where they drive neurotransmission. An increase in dopamine levels is associated with a relief of depressive symptoms.

[Petros Agapetos]

Buproprion is a norepinephrine–dopamine reuptake inhibitor (NDRI), a drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter (NET) and the dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of both norepinephrine and dopamine and, therefore, an increase in adrenergic and dopaminergic neurotransmission. A closely related type of drug is a norepinephrine-dopamine releasing agent (NDRA).

[Herr Abubu]

A psychiatric medication is a licensed psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. Usually prescribed in psychiatric settings, these medications are typically made of synthetic chemical compounds. Since the mid-20th century, such medications have been leading treatments for a broad range of mental disorders and have decreased the need for long-term hospitalization, therefore lowering the cost of mental health care.[1][2][3][4] The recidivism or rehospitalization of the mentally ill is at a high rate in many countries and the reasons for the relapses are under research.[5][6][7][8]

[Herr Abubu]

Fluoxetine, also known by trade names Prozac and Sarafem among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.[1] It is used for the treatment of major depressive disorder, obsessive–compulsive disorder (OCD), bulimia nervosa, panic disorder, and premenstrual dysphoric disorder. It may decrease the risk of suicide in those over the age of 65. Fluoxetine has also been used to treat premature ejaculation. It is taken by mouth.[1]

Common side effects include trouble sleeping, loss of appetite, dry mouth, rash, and abnormal dreams. Serious side effects include serotonin syndrome, mania, seizures, an increased risk of suicidal behavior in people under 25 years old, and an increased risk of bleeding. If stopped suddenly a withdrawal syndrome may occur with anxiety, dizziness, and changes in sensation.[1] It is unclear if it is safe in pregnancy. If already on the medication it may be reasonable to continue during breastfeeding.[5] Its mechanism of action is not entirely clear but believed to be related to increasing serotonin activity in the brain.[1]

Fluoxetine was discovered by Eli Lilly and Company in 1972, and entered medical use in 1986.[6] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[7] It is available as a generic medication.[1] The wholesale cost in the developing world is between 0.01 and 0.04 USD per day as of 2014.[8] In the United States it costs about 0.85 USD per day.[1]

[Herr Abubu]

I've been very educated by this thread. Thank you, Petros Agapetos.

[Petros Agapetos]

I've been very educated by this thread. Thank you, Petros Agapetos.

I have taken some of these drugs, so I am here to share both information and my personal experiences on these meds.

[Ultra]

Fluoxetine, also known by trade names Prozac and Sarafem among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.[1] It is used for the treatment of major depressive disorder, obsessive–compulsive disorder (OCD), bulimia nervosa, panic disorder, and premenstrual dysphoric disorder. It may decrease the risk of suicide in those over the age of 65. Fluoxetine has also been used to treat premature ejaculation. It is taken by mouth.[1]

Common side effects include trouble sleeping, loss of appetite, dry mouth, rash, and abnormal dreams. Serious side effects include serotonin syndrome, mania, seizures, an increased risk of suicidal behavior in people under 25 years old, and an increased risk of bleeding. If stopped suddenly a withdrawal syndrome may occur with anxiety, dizziness, and changes in sensation.[1] It is unclear if it is safe in pregnancy. If already on the medication it may be reasonable to continue during breastfeeding.[5] Its mechanism of action is not entirely clear but believed to be related to increasing serotonin activity in the brain.[1]

Fluoxetine was discovered by Eli Lilly and Company in 1972, and entered medical use in 1986.[6] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[7] It is available as a generic medication.[1] The wholesale cost in the developing world is between 0.01 and 0.04 USD per day as of 2014.[8] In the United States it costs about 0.85 USD per day.[1]

Shit, I never thought about how many women there are out there who take antidepressants while pregnant. That can only have detrimental effects on the baby's brain development. Studies I have looked at suggested that 3 to as much as 13% of pregnant women take antidepressants during their pregnancy, with correlated detrimental effects on baby development with use of antidepressants!!! Just shocking.

It is estimated that the prevalence of depression during pregnancy is 7% to 13%,1 and 3% to 13% of pregnant women are treated with antidepressants, most commonly selective serotonin reuptake inhibitors (SSRIs).2–4 Antidepressants can effectively control mood and reduce the risks of serious consequences associated with untreated depression for both the mother and her offspring.5 However, use of antidepressants during pregnancy has been associated with adverse pregnancy outcomes. First trimester exposure to certain SSRIs has been associated with some specific birth defects,6–8 whereas use of SSRI and non-SSRI antidepressants, particularly later in pregnancy, has been associated with preterm delivery,9–14 low birth weight,11,12 birth weight small for gestational age (SGA),15,16 gestational hypertension and preeclampsia,17 and various neonatal complications.9–13,18–20 Evidence on the effects of maternal antidepressant use on gestational length and fetal growth, however, is conflicting,21 as some studies did not find such effects.22–27

Although not as dramatic as major birth defects, preterm delivery and fetal growth restriction are leading causes of perinatal mortality and morbidity28,29 and are associated with enormous societal burdens.30 Previous studies often had certain limitations,21 including small sample sizes that limit the power to detect an effect,25–27 inadequate control of potential confounding by lifestyle factors such as cigarette smoking and alcohol intake,10,12,15,26 limited information on exposure timing,10 or potential selection bias with the inclusion of women who actively sought reproductive safety information regarding antidepressant use and whose risks of adverse perinatal outcomes might be different from other antidepressant users.9,22–24,26 This study was undertaken to assess the relation between antidepressant use and both preterm delivery and SGA.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206605/