studied byStudied by 2 people
get a hint

neurotransmitters included in depression

1 / 106

Tags and Description

107 Terms


neurotransmitters included in depression

  • Noradrenaline

  • Dopamine

  • Serotonin

  • Histamine

New cards

Origin of Noradrenaline

Locus coeruleus

New cards

Origin of Dopamine

Substantia nigra + VTA

New cards

Origin of Serotonin

Raphe nuclei

New cards

Origin of Histamine

Hypothalamus with tuberomammillary complex

New cards


50% reduction in symptoms

New cards


all symptoms relieved (to 6 months)

New cards


remission longer than 6-12 mths

New cards


symptoms worsen before recovery (<6-12 mths)

New cards


symptoms worsen after recovery (>12 mths)

New cards

patients given anti depressants respond in how many days/wks?

67% patients respond in 8 wks

New cards

give stats of these 67% ppl when kept on/taken off drug

  • Taken off

    • 50% of 67% ppl (33%) will retain the effects for a year

    • other half will become depressed again in one year

  • Kept on

    • 10-15% relapse again in a year

    • 85% remain well

New cards

what happens when patient is given placebo instead of medication in the first place?

  • 33% responders

  • 67% non - responders

New cards

Monoamine hypothesis

depression is caused due to deficiency in one or more of the 3 catecholamines = serotonin, norepinephrine or dopamine

New cards

mechanism of antidepressant medication

Need to increase the levels of one/combination of these hormones by:

  • blocking their reuptake pumps

  • inhibiting their oxidation by monoamine oxidation (MAOs)

New cards

reuptake pump is responsible for what

decreases the level of serotonin available to post-synaptic membrane by taking up the serotonin back inside the axon terminal

New cards

MAO function

  • responsible for degradation of catecholamines in the CNS

  • present both in cleft and within the axon terminal

New cards

problems with the monoamine hypothesis

  • no antidepressant effect observed for certain drugs that increase the NTs (cocaine, methamphetamines)

  • long delay (2-3 wks) between increase in NTs and clinical effect

  • decreased levels of NTs have only been associated with only some types of depression

New cards

serotonin functions

  • results in neurotransmission

  • changes the proteins made in neurons

New cards

what are the effects of the neuronal proteins serotonin acts upon

  • responsible for long-term effect of antidepressants on mood

  • facilitate increased neurogenesis, therefore helps in improvements in behavioral/mood disorders

New cards

4 points about Brain-derived Neurotrophic Factor (BDNF)

  • normally regulated by cell body of neuron by factors like monoamines, glutamates, other signals

  • can be reduced by stress

  • during depression ↓MAs = ↓BDNFs

  • responsible for allowing neurons to make new connections; consequence of this = improves depression

New cards

does hippocampus become small or big during depression? why?

  • becomes small

  • bc the peptide factors are low

New cards

what does amygdala do?

  • part of limbic system

  • associated w emotions like anger, pleasure, sorrow, fear and sexual arousal

New cards

what effect does medication have on amygdalas of depressed indv?

  • olume medicated = amygdala vol ↑es

  • unmedicated = amygdala vol ↓es

New cards

name diff classes of antidepressant drugs

  • MAO inhibitors = Classical (MAOi), Reversible (RIMA)

  • Tricyclic antidepressants

  • SSRI (Serotonin Selective Reuptake Inhibitors)

  • NDRI (Noradrenaline/Dopamine reuptake Inhibitors)

  • SNRI (Serotonin/Noradrenaline Reuptake Inhibitors) (Noradrenaline/Serotonin Specific Antagonists - NaSSR)

  • SARI (Serotonin Antagonists/Reuptake Inhibitors)

For bipolar disorder -

  • Lithium

  • Valproic Acid

New cards

first clinically discovered antidepressants?


New cards

2 subtypes of MAOs?

  • MAO A

  • MAO B

New cards

examples of MAOis

  • phenylzine (Nardine)

  • tranylcypromine (Parnate)

New cards

Features + side effects of classical MAOis

  • non-selective = blocks both subtypes

  • irreversible inhibitors = this is why action is long lasting and ∴ takes considerable time to regenerate MAOs again

  • has severe interaction with food, drugs and wine

    • tyramine

    • drugs = TCA, sympathomimetic (both ↑es bp to vvvvv ↑↑↑↑ levels)

    • meperidine (Demerol) = fever

  • bc of so many side effects these drugs were no longer used

New cards

Tyramine features

  • helps to regulate bp

  • acts as a sympathomimetic when ingested

New cards

what is a sympathomimetic

mimics/stimulates adrenergic NS = raises bp to alarming levels

New cards

Tyramine is present in (food items)

  • cheese

  • beer

  • liver

New cards

Effect of MAOs on tyramine

helps in breaking down excess tyramine in body

New cards

Effect of MAOis on tyramine in body

  • blocks tyramine

  • spikes bp

New cards

explain tyramine + MAOi effect in detail

  • Tyramine ↑es release of NE

  • Irreversible MAOi-A inhibits MAO to break down tyramine to stop NE destruction

  • ↑es NE = can lead to dangerous elevations of bp => hypertension

New cards

3 subtypes of MAOis?

  • Classical MAOis

  • MAO A specific inhibitors

  • MAO B inhibitors

New cards

MAOi A features

  • metabolises MAOs closely related to depression => NA,5HT

  • reversible inhibitors

  • E.g. = Moclobemide

    • reversible, competitive inhibitor

    • removes tyramine effect danger

New cards

MAOi B features

  • involved in metabolism of DA + protoxins (which become toxins when activated)

  • used in treatment of Parkinson’s

New cards

5HT receptors can be found in

  • CNS

  • Blood vessels

  • Smooth muscle

  • Platelets

  • GI tract

New cards

side effects of MAOis

Serotonin syndrome

  • excessive levels of 5HT

  • mild symptoms = ↑sed heart rate, sweating, dilated pupils, over responsive reflexes

  • moderate symptoms = high bp, hyperthermia; Mental changes = hypervigilance, agitation

  • severe symptoms = severe ↑se in heart rate + bp leading to shock

New cards

TCA features

  • first tested as antipsychotics

  • block uptake of NA, 5HT, and DA

  • have many f gps

    • α1 adrenergic-R = antagonism

    • histamine1-R = antagonism

    • ACh muscarinic-R = antagonism

    • 5HT and NA = reuptake inhibition

  • 5HT and NA levels ↑se = depression lifts

New cards

TCA function

  • ↑se level of NT retained in synaptic cleft by blocking reuptake pump

New cards

TCA side effects

  • histamine-1 antagonism = ↑ appetite, ↓ metabolism causes weight gain + drowsiness

  • cholinergic (muscarinic) antagonism = constipation, blurred vision, dry mouth, drowsiness

  • α1 adrenergic antagonism (less extent) = dizziness, drowsiness, ↓sed bp

New cards


  • when receptors for own NT are present on presynaptic neuron which results in inhibition of the NT release

  • e.g., histamine autoreceptors

New cards

mechanism of inhibition of autoreceptors

  • GPCRs linked by G proteins to an inward K+ rectifying channel

  • prevents depolarisation

  • inhibits NT release

New cards


  • receptor for a MA diff from the NT made by the neuron is present on it

  • activation inhibits NTission from the neuron

  • e.g., non-histaminergic neuron

New cards

effect of serotonergic neurons

  • project to higher brain centers

  • affects mood and has effects on secondary NTission

New cards

how were SSRIs formed

  • by removing α1, muscarinic, histaminergic and NA reuptake blocker activities from TCA

  • only SRI was kept

New cards

what normally happens in depressed ppl

somato-dendritic release of 5HT in raphe nuclei

  • SERT (serotonin transporter) takes up 5HT

  • 5HT1A dendritic autoreceptors take up 5HT to inhibit firing of serotonergic receptors

  • Axon collateral release of 5HT

  • serotonin available in the synaptic space ↓ses

  • hence depression

New cards

mechanism of SSRI

  • binds to SERT, blocks it

  • ↑ses serotonin in somatodendritic region

  • downregulates 5HT1A receptors and hence they ↓se in no.

  • neuron gets disinhibited

  • firing rate of serotonin in synaptic space ↑ses

New cards

reason for delayed onset of action of SSRIs

  • downregulation is mediated by genomic mechanisms

  • hence reduction of 5HT1A receptors is not immediate

  • ∴ delay in producing ↑se in serotonin at terminals occurs

  • hence delay in therapeutic effects/onset of action

New cards

Neurogenic hypothesis

new neurons in adult brain needed for proper mood control + for antidepressant efficacy

New cards

most prescribed class of antidepressants


New cards

examples of SSRIs

  • fluoxetine - Prozac = long half-life (~ 4 days) same effect, less drug

  • sertraline - Zoloft

  • paroxetine - Paxil

  • citalopram - Celexa

New cards

advantages of SSRIs

much much much safer than MAOis and safer than TCAs for overdose

New cards

side effects of melatonin

  • disturbed circadian rhythm

  • nausea, anorexia, insomnia, sexual dysfunction

  • possibly ↑ed suicidal thoughts in young adults

New cards

how do SSRIs disturb the circadian rhythm

  • serotonin = precursor to melatonin

  • in presence of SSRIs = 5HT is reduced in neuron and is instead synthesised and released

  • ∴ less of it is available for production of nor melatonin

  • ∴ less melatonin

New cards

features of NDRI

  • used to stop smoking bc = ↑sed dopamine levels help in reducing craving

  • e.g., bupropion = Wellbutrin, Zyban

New cards

side effects of NDRIs

  • feeling of restlessness

  • high bp

New cards

features of SNRI

  • inhibit reuptake of 5HT, NA and some DA

  • effects on reuptake NTs vary acc to dose = 5HT → NA → DA

  • claim to produce more rapid effect = 1 wk

  • e.g., venlafaxine = Effexor

New cards

side effects of SNRIs

  • nausea

  • dizziness

New cards

what is disinhibition

antagonists of a heteroreceptor prevent inhibitory effects of the agonist

New cards

SNDI features

  • α2 antagonists = block α2 receptor-mediated -ve feedback inhibition (essentially blocks both auto and heteroreceptors to)

  • ↑se release of NA and 5HT

New cards


presynaptic + dendritic autoreceptor for serotonergic neurons

New cards

5HT1A, 5HT2A/B

postsynaptic stimulatory receptor

New cards


postsynaptic stimulatory heteroreceptor on adrenergic and dopaminergic neurons

hence, inhibit NTission

New cards

mechanism of action of SNDIs/NaSSAs + example

boosts NTs 5HT and NE by:

  • blocking α2 adrenergic presynaptic autoreceptor

    • ↑ses NE NTission (disinhibition)

  • blocking α2 adrenergic presynaptic receptor on 5HT neurons (heteroreceptors)

    • ↑ses 5HT NTission

  • E.g., Mirtazapine

New cards

what do SNDIs also acts as and how

  • act as NaSSAs by blocking certain 5HT receptors (helps prevent many side effects)

    • 5HT2C antagonist = more NA secretion → anxiolytic

    • 5HT2A + 5HT2C antagonist = reduces insomnia, sexual dysfunction

    • 5HT3 antagonist = reduces nausea and GI upset

  • blocks H1 receptors to reduce insomnia

New cards

how do SARIs work

  • highly sedating = excellent non-dependence, hence hypnotic

  • has v little α1, H1 and HT2A+C antagonism + SRI

  • ↑se 5HT levels + block 5HT2A+C which are resp for side effects caused by excess 5HT present

  • combining SRI with 5HT2A+C antagonism leads to antidepressant function w/o sexual dysfunction, anxiety, or insomnia

  • dosing of the drug will determine if its primarily pro-sleep (hypnotic) (25-150mg) or antidepressant (150-600mg)

  • e.g., Trazodone

New cards

how does combining SRI with 5HT2A+C antagonism in SARIs prove to be helpful

  • combining SRI with 5HT2A+C antagonism leads to antidepressant function w/o sexual dysfunction, anxiety, or insomnia

  • dosing of the drug will determine if its primarily pro-sleep (hypnotic) (25-150mg) or antidepressant (150-600mg)

New cards

what will happen if SARI trazodone if combined w SSRIs/SNRIs?

  • can potentially treat insomnia + anxiety associated w depression itself ++ prevent it too caused by more 5HT

New cards

side effects of SARIs

  • low level of α1 antagonist activity = can cause hypotension

  • metabolite is active

    • trazodone is converted into active metabolite called meta-chloro-phenyl piperazine (mCPP)

  • has high affinity for 5HT2A+C, 5HT1A

    • acts mostly as agonists in these

    • can result in anxiety in some

New cards

two mood stabilisers (simply used for maintenance in bipolar)

  • lithium

  • valproic acid

New cards

how does Li work as a mood stabiliser


  • Li enters via Na channel

  • blocks both inositol phosphatase that dephosphorylates

    • IP2 → IP1

    • IP1 → free inositol

  • hence blocks inositol signaling cascade in brain

  • blocks regeneration of PIP2

  • affects central adrenergic, muscarinic and serotonergic NTission

  • promotes GABA-ergic NTission

New cards

features of Li as mood stabiliser

  • mainly used as prevention + maintenance for bipolar (not for people at the height of mania)

  • long half-life

  • narrow therapeutic window → hence patients have to be highly monitored

  • anxiety is treated by

    • ↓se in NE effects

    • ↑se in 5HT effects

New cards

side effects of Li

  • nausea

  • polyuria (↑se in peeing) + thirst

  • tremor

New cards

Valproic acid features

  • elevation of GABA conc

  • inhibition of neuronal voltage-gated Na+ channels

  • act as anticonvulsants

  • highly effective

  • 1st choice for

    • rapid cycling

    • mixed mania

    • mania w hallucinations

    • delusions

    • an option if patient cannot tolerate side effects of Li

New cards

anxiety (physical) symptoms

headache, sweating, palpitations, dyspepsia, etc., all in rxn to a perceived threat which is vague, internal + unknown

New cards

what causes anxiety, panic attacks, tremors, etc

monoamines from locus coeruleus activate the amygdala which causes these

New cards

how do you inhibit activation of amygdala

by using benzodiazepines (GABA)

New cards

most abundant inhibitory NT in CNS

GABA = amino butyric acid

New cards

what is GABA synthesized and destroyed by

synthesize = from glutamate via glutamic acid decarboxylase

destroy = by GABA transaminase

New cards

BZD potentiate activation of what

GABA A receptors

New cards

BZD are +ve/-ve AMs?

+ve = PAMs

New cards

how do BZD act as PAMs for GABA A receptors

binds to allosteric site on receptor and ↑ses action of GABA A receptors, hence PAMs

New cards

3 types of anxiolytics?

  • GABAergic

    • benzodiazepines

    • non benzodiazepines

  • Serotonergic

  • Noradrenergic antagonist

New cards

BZD features

  • ↑ses effect of endogenous GABA

  • uses

    • reduction of anxiety + aggression

    • sedation + induction of sleep

    • muscle relaxants (central action)

    • as antiepileptic drugs

  • bind to GABA A α subunits: α 1, 2, 3 & 5

    • all are associated with diff effects and hence they have wide range of effects

  • E.g., Diazepam (Valium), Lorazepam (Ativan), Clonazepam

New cards

what does Diazepam metabolize into? how does that help?

  • metabolises into active metabolite called Nordazepam

  • active metabolite has has longer half-life (bc its still biologically active)

New cards

what is VLPO

  • Ventrolateral Preoptic Nucleus of the Hypothalamus (sleep center)

New cards

2 main effects of BZD

  • anxiolytic effect = inhibit activation of amygdala by binding to the GABA A receptors in the amygdala

  • hypnotic effect = promote sleep by binding at GABA A-R in VLPO, causing sleepiness

New cards

how does BZD affect sleep badly

ppl don’t get restful nights sleep on these, since they just induce sleep

stage 4 of deep sleep is never reached

New cards

side effects of BZD

  • excessive drowsiness

  • ataxia (bc regular NTission of motor neurons is inhibited)

  • Dependence, tolerance (14) days and abuse

    • prolonged usage results in withdrawal

  • dangerous when combined w alcohol

  • possible anterograde amnesia

New cards

non BZD features

  • rapidly becoming 1st line treatment of insomnia

    • induce sleep but don’t disrupt sleep cycle like BZD

  • demonstrate less unwanted cognitive, memory and motor side effects

  • better pharmacokinetics

  • rapid onset and short duration of action

  • e.g., zaleplon, zolpidem, zopiclone

New cards

how does Zaleplon and Zolpidem aid as hypnotics

are α1 selective hypnotics

  • bind selectively to α1 subunit (sleep) of GABA A receptors

  • this subunit is imp for sedation and possibly for anticonvulsant and amnesic actions

New cards

features of serotonergic anxiolytics

  • less sedative

  • less interaction w alcohol

  • less potential for abuse

  • there is delay in onset of action

  • E.g., Buspirone

    • 5HT1A partial agonist

    • interacts w somatodendritic -ve feedback receptors

    • ↓es release of 5HT by stimulating -ve feedback in controlled fashion

New cards

side effects of serotonergic anxiolytics

  • vertigo

  • “woozy” feeling

    • probably due to interactions w postsynaptic 5HT1A receptors

New cards

Noradrenergic anxiolytics features

  • reduces symptoms like = anxiety, tachycardia, dilated pupils, tremors, sweating

  • α2 agonist, e.g., clonidine

    • useful in reducing these symptoms

    • not v effective in reducing the emotional aspects of anxiety

  • β adrenergic antagonists, e.g., propranolol

    • useful in treatment of social phobia, stage-fright type of anxiety + anxiety associated w the memory of stressful events

New cards

street drugs

  • anxiolytics

    • flunitrazepam = Rohypnol

    • GHB

  • Sympathomimetics

    • MDMA = ecstasy

    • Methamphetamine

    • Methylphenidate

  • Anesthetic

    • Ketamine

New cards

flunitrazepam/Rohypnol (roofies) features

bzd used for

  • short-term treatment of insomnia

  • sedative hypnotic

  • preanesthetic medication

physiological effect is similar to diazepam but 10x more potent

New cards


  • gamma hydroxybutyric acid

  • occurs naturally in mammalian brain

  • acts on GABA + GHB receptors, either directly or by converting GHB to GABA

  • synthesis = mixing gamma butyrolactone + NaOH is proper amts

  • often tinted blue with food coloring

  • danger lies in = possibility of ingesting impurities or unreacted substrates

New cards

Explore top notes

note Note
studied byStudied by 11 people
Updated ... ago
5.0 Stars(1)
note Note
studied byStudied by 24 people
Updated ... ago
5.0 Stars(1)
note Note
studied byStudied by 70 people
Updated ... ago
5.0 Stars(4)
note Note
studied byStudied by 236 people
Updated ... ago
5.0 Stars(4)
note Note
studied byStudied by 4 people
Updated ... ago
5.0 Stars(1)
note Note
studied byStudied by 5 people
Updated ... ago
5.0 Stars(1)
note Note
studied byStudied by 23 people
Updated ... ago
5.0 Stars(1)
note Note
studied byStudied by 3120 people
Updated ... ago
4.7 Stars(17)

Explore top flashcards

flashcards Flashcard32 terms
studied byStudied by 188 people
Updated ... ago
5.0 Stars(2)
flashcards Flashcard622 terms
studied byStudied by 11 people
Updated ... ago
5.0 Stars(1)
flashcards Flashcard103 terms
studied byStudied by 5 people
Updated ... ago
5.0 Stars(1)
flashcards Flashcard43 terms
studied byStudied by 28 people
Updated ... ago
5.0 Stars(2)
flashcards Flashcard42 terms
studied byStudied by 6 people
Updated ... ago
5.0 Stars(1)
flashcards Flashcard67 terms
studied byStudied by 111 people
Updated ... ago
5.0 Stars(1)
flashcards Flashcard79 terms
studied byStudied by 6 people
Updated ... ago
5.0 Stars(1)
flashcards Flashcard37 terms
studied byStudied by 19 people
Updated ... ago
5.0 Stars(1)