15. Dopaminergic, Serotonergic neurotransmission Flashcards
Biosynthesis of catecholamines
-> List the steps
What is the inhibitor of DOPA decarboxylase?
PLP (B6 vitamine)
What is the role of α-Methyldopa?
It gives rise to false transmitter (α-methylnoradrenaline), which is a potent α2 agonist, thus causing powerful presynaptic inhibitory feedback (also central actions).
-> Its use as an antihypertensive agent is now limited mainly to during pregnancy.
Role of dopamine in schizophrenia
- Original dopamine theory was proposed by Carlsson
on the basis of indirect pharmacological evidence in humans and experimental animals - Amphetamine releases dopamine and produce in humans a
behavioural syndrome indistinguishable from schizophrenic episode - Hallucinations are a side effect of L-dopa therapy for Parkinson’s disease
Role of glutamate in schizophrenia
In humans NMDA receptor antagonists can produce both positive and negative symptoms
What is so special about HT-5 monoamine receptors?
of all the currently identified monoamine receptors,
only 5-HT 3 is an ionotropic receptor belonging to the
nicotinic acetylcholine superfamily of pentameric receptors
How does Serotonin synthesis occur?
Characteristics of Tryptophan hydroxylase
*only in serotoninergic neurons
*rate limiting
*not saturated
Distribution of Serotonin synthesis
*Gastrointestinal tract (chromaffin cells and enteric neurons) (90%)
*Platelets (accumulate it from the plasma and release it when they aggregate)
*Central Nervous System
Actions and functions of 5-hydroxytryptamine
*increased gastrointestinal motility
(direct excitation of smooth muscle and indirect action via enteric neurons)
*contraction of other smooth muscle (bronchi, uterus)
*mixture of vascular constriction (direct and via sympathetic innervation)
and dilatation (endothelium dependent)
*platelet aggregation
*stimulation of peripheral nociceptive nerve endings *excitation/inhibition of central nervous system neurons.
What are some Clinical conditions
associated with disturbed 5-hydroxytryptamine function
migraine
mood disorders
anxiety
pulmonary hypertension (SSRI)
valvular heart disease
(5HT2B serotonin receptor agonists)
serotonin toxicity
carcinoid syndrome
The biosynthesis and catabolism of serotonin
-> Identify
The role of 5-HIAA assay: neuroendocrine neoplasms
Detecting carcinoid tumors and monitoring their progression
Where is Melatonin synthesized?
Melatonin is synthesised exclusively in the glandula pineale, an endocrine gland that plays a role in establishing circadian rhythms.
The role of enzymes in glandula pineale, an endocrine gland?
The gland contains two enzymes, not found elsewhere, which convert 5-HT by acetylation and O-methylation to melatonin, its hormonal product.
What are receptors for Melatonin?
MT1 and MT2
What are the agonists of melatonin?
insomnia, depression (improves mood, sleep pattern)
Melatonin secretion is high at (1)___ and
low by (2)___.
- night
- Day
Melatonin secretion is high at night and
low by day. This rhythm is controlled
by ___
input from the retina via a noradrenergic retinohypothalamic tract that terminates in the suprachiasmatic nucleus (SCN) in the hypothalamus
Melatonin
-> identify
5-HT N-acetyl transferase
What does this slide indicate?
Presynaptic neurons of serotonin neurotransmisson
What does this slide indicate?
Presynaptic neurons of norepinephrine neurotransmisson
The substituted amphetamines inhibits the transport of 5-HT by ___ and _____
both (A) the vesicular transporter and (B) the serotonin transporter (SERT).
Serotonergic neurotransmission and pharmacological interventions
-> What are the inhibitors for depression treatment?
Monoamine Oxidase Inhibitors
Tricyclic antidepressants
Serotonin and Noradrenaline Uptake Inhibitors (Snris) Selective serotonin reuptake inhibitors
Serotonin syndrome caused by ___
medications (SSRI) cause high levels of serotonin to accumulate in the body.
Increased dose of a drug that affect serotonin metabolism
Drug interactions
Certain illicit drugs and dietary supplements
Therapy for Serotonin syndrome
5HT-receptor blocker
What are some Antipsychotic effects (schizophrenia)
Dopamin theory (amphetamine, D2 agonists: similar symptoms, but not every symptom)
Glutamate theory (NMDA receptor antagonists, phencyclidine (PCP))
hallucinogen drugs (LSD) - 5-HT2 receptor agonists
5-HT2 receptor inhibitors (effect also on DA receptors)
The role of 5-HT3 receptor antagonists
preventing and treating the vomiting, nausea
(postoperative or caused by radiation therapy or administration of cytotoxic drugs such as cisplatin.)
