This document discusses serotonin synthesis and degradation. It notes that tryptophan is converted to 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase, and 5-HTP is then converted to serotonin by 5-hydroxytryptophan decarboxylase. Serotonin is broken down by monoamine oxidase. It also discusses the roles of various serotonin receptors, including that 5-HT1A receptors accelerate dopamine while 5-HT2A receptors act as a brake on dopamine. Finally, it concludes that glutamate acts as an accelerator or brake on dopamine depending on the brain area, and that atypical antipsychotics can decrease dopamine in some areas through dual actions

1. SEROTONIN NT
By: Asmaa Zidan Ali
31/10/2016

2. Smith et al (1997)
Synthesis and degradation of
serotonin
Tryptophan
5-Hydroxytryptophan (5-
HTP)
Tryptophan hydroxylase
5-Hydroxytryptamine (5-
HT)
5-Hydroxytryptophan decarboxylase
5-Hydroxyindolacetic
acid (5-HIAA)
Monoamine oxidase (MAO)

3. Serotonin synthesis
Serotonin
termination

4. False
substrate
Endogenous
substrate
Gene familyCommon
abbreviation
transporter
ecstacy
(MDMA)
serotoninSLC6SERTserotonin
transporter
dopamine
epinephrine
amphetamine
NorepinephrineSLC6NETnorepinephrine
transporter
norepinephrine
epinephrine
amphetamine.
dopamineSLC6DATdopamine
transporter

6.  5HT1A receptors are accelerators of dopamine through:
1. Inhibition of serotonin neuron (disinhibition of dopamine)
2. Brake on glutamate & GABA
 5HT2A receptors are brake to dopamine through:
1. Inhibition of dopamine neuron directly
2. Stimulation of glutamate & GABA

7. Serotonergic Receptors
5‐HT2 receptor stimulation 5‐HT3 receptor stimulation
• Agitation
• Insomnia
• Sexual dysfunction
• Satiation
-5‐HT2A receptor normally works to inhibit (brake)
the release of the neurotransmitter dopamine.
So, 5-HT2A antagonism – suppression of EPS
• Nausea
• Diarrhea
• Headache
• 5HT1A is dopamine accelerator. However, 5HT2A is
dopamine brake (opposite effect is on glutamate).
So, 5-HT1A agonism – effects on cognitive symptoms,
suppression of EPS
5-HT2A antagonism – suppression of EPS

8. DA
D1
D2
Caudate/putamen
Normal function
Sunstantia nigra
pars
compacta
5-HT2A
-
5-HT
Raphe
Role of 5-HT in Nigrostriatal Dopaminergic Synapse
Nigrostriatal tract

9. Glutamate acts as accelerator on dopamine
in mesocortical area, and act as a brake
in mesolimbic area.

10. Basic Conclusion
 Glutamate acts as accelerator on dop. in mesocortical area.
 Glutamate acts as brake on dop. in mesolimbic area.
 5HT 1A acts as accelerator on dop.
 5HT2A acts as brake on dop.
 5HT 1A acts as brake on glutamate.
 5HT2A acts as accelerator on glutamate.
So, atypical antipsychotics (mainly serotonergic, can
decrease dopamine in mesolimbic area by 2
mechanisms 1st:
it’s brake effect on dopamine through 5HT2A, and the 2nd
is it’s accelerator effect on glutamate which is brake on
dopamine).
 Serotonin and dopamine have reciprocal roles in the
regulation of prolactin secretion (D2 inhibits prolactin,
Serotonin promotes prolactin).


11. Duloxitine Atomoxeti
ne
Reboxetine Dapoxetine
SNRI selective
norepineph
rine
reuptake
inhibitor
Selective
norepineph
rine uptake
inhibitor
Not FDA
approved
yet
30,60, =
Joypox tab
ultrshort
acting SSRI
for treatment
of premature
ejaculation.

12. THANK YOU