Download Невротрансмитери в ЦНС

Невротрансмитери
в ЦНС
(Резюме)
Доц. д-р Иван Ламбев
(www.medpharm-sofia.eu)
Many of the drugs acting on the CNS exert their effects
through the modication of chemical transmission. A large
number of neurotransmitters have been identified in CNS:
● glutamate
● aspartate
● γ-aminobutyric acid (GABA)
● glycine
● noradrenaline, adrenaline
Catecholamines
● dopamine (DA)
● 5-hydroxytryptamine (5-HT, serotonin)
● acetylcholine (ACh)
● histamine
● melatonin, orexin and others
Glutamate is the excitatory amino acid transmitter
in the CNS. It acts at NMDA (N-methyl-D-aspartate)
and other receptors. NMDA receptors are involved
in the development of adaptive responses that
modulate synaptic transmission, known as synaptic
plasticity.These responses have a role in both
physiological (e.g. learning) and pathological
processes (e.g. facilitation of central nociceptive
transmission in chronic pain states). The dissociative
anesthetic ketamine blocks the channel associated
with the NMDA receptor.
The principal inhibitory neurotransmitter
in the CNS is GABA. There are two types of
GABA receptors: GABAA and GABAB.
The benzodiazepines owe their sedative action
to facilitation of this inhibitory neurotransmitter,
binding to a discrete site on the GABAA receptor.
Glycine is primarily an inhibitory transmitter
found in the gray matter of the spinal cord.
Noradrenergic transmission in the CNS is important
in control of alertness and mood and in the regulation
of blood pressure. Adrenoceptors are recognized
and further divided into subtypes, i.e. α1, α2, β1, β2
and β3. While noradrenaline (NA – norepinephrine)
appears to have an inhibitory effect on individual
brain cells, mediated primarily via β-receptors,
excitatory effects may also be observed at both αand β-receptors. The α2-agonists
owe their sedative action
to effects on central
Noradrenaline
noradrenergic transmission.
Dopamine (DA), a precursor of NA, has a role in
the control of movement and behavior. There are
two families of DA receptor: D1 and D2. The D2 group
appears important in the CNS and comprises D2, D3
and D4 receptors. The D1 group is subdivided into
D1 and D5 receptors. The sedative action of the
phenothiazines and the butyrophenones has been
ascribed to DA antagonism, primarily at the D2 family
of receptors. Since DA-ergic neurones are also
involved in the production of nausea and vomiting,
these drugs have additional antiemetic activity
Acetylcholine
Functions associated with acetylcholine in the
CNS include arousal, learning, memory and
motor control. Muscarinic receptors appear to be
more important, although nicotinic receptors are
also present. The effects of acetylcholine are
mostly excitatory, although inhibition may be seen
at some central muscarinic receptors.
Histidine
CO2
Histamine
CH2
HN
N
ИмидазолN-метилтрансфераза
Метилимидазол
Оцетна киселина
H2 C
NH2
In the CNS have been identified H1, H2 and H3
histaminic receptors. In CNS histamine is involved
in the control of wakefulness, since H1-receptor
antagonists induce sedation as a side effect.
The phenothiazines have variable H1-receptor
blocking activity.
CH2
HN
N
H2C
NH2
Rang et al.
Pharmacology
– 5st Ed. (2003)
HO
CH2 H2C NH2
NH
indol derivative
Serotonin
(5-Hydroxytryptamine: 5-HT)
Tryptophan
5-hydroxytryptophan
CO2
5-HT (serotonin)
HO
CH2 H2 C
NH2
NH
МАО
Алдехиддехидрогеназа
5-хидроксииндол оцетна киселина
Богати на 5-HT са:
•СЧТ (хромафинни клетки
и ентерични неврони)
•Тромбоцити
•ЦНС
5-НТ КОНТРОЛИРА:
•апетита
•повръщането
•болковата перцепция
•съня, настроението, волята
•халюцинаторната активност
5-HT УЧАСТВА В
ПАТОГЕНЕЗАТА НА:
•мигрената, депресиите
•психомоторната възбуда
•шизофренията (с DA)
•карциноидния синдром
(малигнен тумор на чревните
ентерохромафинни клетки)...
(NE)
(5-HT)
(DA)
The effects of DA, 5-HT and NE on the brain functions
Melatonin is the hormone
produced by the pineal gland
during darkness. It is released
mainly at night. The impressive
nature of the diurnal rhythm in
melatonin secretion has stimulated interest in its use
therapeutically to reset circadian rhythm to prevent
jet-lag on long-haul flights and for blind or partially
sighted people who cannot use daylight to
synchronize their natural rhythm. Melatonin is a
potent inhibitor of DA release and its release
appears to be linked with endogenous opioids.
Орексинът (хипокретин) се секретира от малък
брой неврони (около 10 000 до 20 000), локализирани
в хипоталамуса. Орексинови рецептори има обаче
в повечето аксони на главния и гръбначния мозък.
Орексинът е невротрансмитерен пептид, регулиращ
будността, съня и апетита.
При деструкция на клетките, продуциращи орексин,
се развива нарколепсия и силно отслабване на
мускулния тонус (каталепсия).
Препаратът Suvorexant (Belsorma) потиска
орексиновите рецептори и се използва като хипнотик.
Ендотелини - мощни
дългодействащи
вазоконстриктори
ЕТ-1, ET-2 и Е3
ЕТА-рецептори: >>> вазокострикция
ЕТB-рецептори: 30 s вазодилатация
Плазмените нива на ЕТ-1 нарастват
при вазоспазъм и ОМИ.
Cholecystokinin (CCK) невропептид, медииращ
паническите реакции
ANP
CGRP
SP
NPY (c NA)
VIP
(с ACh)
ОПИОИДНИ ПЕПТИДИ