Drugs Affecting Neurotransmission Flashcards
(37 cards)
CNS Disorders Associated with Too Much NT activity
Epilepsy
Anxiety
Schizophrenia (+)
CNS Disorders Associated with Too Little NT activity
Depression (serotonin)
Parkinson’s (low dopamine in nigrostriatal pathway)
Schizophrenia (-)
Obesity?
Issues with treating NT Conditions
- Multiple receptor types for each NT (lots of side effects)
- Upregulation and downregulation in response to drug treatment
- BBB stops drugs crossing
Drugs that Alter NT Synthesis
L-DOPA (gives more precursor)
a-methyldopa (false neurotransmitter)
L-DOPA
Precursor for dopamine. Increases dopamine. [Parkinsons]
Given with carbidopa which inhibits dopa decarboxylase preventing L-DOPA conversion to dopamine outside of the brain (DA can’t cross BBB) only as it can’t cross BBB, ensuring L-DOPA only targets the brain dopamine levels
a-methyldopa
Converted to a-methylnoradrenaline. Packaged and released as NA would be.
Not a strong agonist of ARs so lowers response that would occur if NA was to bind.
Activates presynaptic a2 ARs = negative feedback mechanism of NA thinks there is lots. [Hypertension]
Drugs Altering Storage
[Less NT packaged into vesicles for release]
Tetrabenazine inhibits VMAT2
Methamphetamine reverses function of VMAT2
Tetrabenazine
Inhibits VMAT2 less noradrenaline, adrenaline, dopamine in vesicles.
Less released upon AP. Depletion of DA treated hyperkinetic movement disorders (Huntington’s Disease)
Methampthetamine
Reverses action of VMAT2.
NT released into cytoplasm. Leaks out through transports DAT, NET, SERT activating postsynaptic receptors without neuronal stimulation.
Drugs Altering Release
Affect fusion of vesicles to membrane and thus release.
Botulinum Toxin at neuromuscular and autonomic nerve junction.
Botulinum Toxin General
Clostridium Botulinum produces.
LD50=0.2ng/kg
Damage is irreversible new nerves needed to be sprouted.
Cosmetically reduces wrinkles.
Medically hyperhidrosis, migraine, lazy eye.
BoNT M.O.A
When endocytosed, cleaves SNARE proteins preventing fusion of NT vesicles to presynaptic membrane. Thus can’t be released.
Acetylcholine for nicotinic receptors. Paralysing muscle fibres.
B,D,F,G= synaptobrevin
A,C,E= SNAP-25
C= Syntaxin
Alter Action at Receptors
Agonists (mimic NT)
Antagonists (block/reduce NT)
Modulators (modulate receptor response)
Agonists of NT receptors
Opioid/opiate drugs on Mu opioid receptors.
Ropinirole at dopamine D2 receptor.
Bromocriptine at D2 receptor.
Apomorphine at D1 and D2 receptor.
Opioid/Opiate Drugs
e.g. morphine, dimorphine(heroin), pethidine, codeine(pro drug of morphine)
GPCRs Ga-i/o =inhibitory [decrease cAMP decrease Ca2+]
Less Ca2+ reduces release of other NTs, neuromodulatory effect.
Other open K+ channels hyperpolarization.
Reduce release of glutamate and substance P (pain transmission), inhibitory effect.
Ropinirole
For Parkinsons loss of neurons of nigrostriatal pathway.
Given with domperidone antagonist of D2 receptors stops agonist action outside of CNS (chemoreceptor trigger zone [sickness]). Can’t cross BBB. Gives selectivity.
Bromocriptine and Apomorphine
Parkinson’s treatment
Activation of other dopaminergic pathways can cause Schizophrenia like symptoms
Antagonists of NT receptors
Domperidone is a D2 antagonist.
Naloxone opioid antagonist.
Antipsychotic drugs (neuroleptics)
Domperidone
Parkinson’s adjunct.
Chemoreceptor trigger zone (CTZ) blocker for sickness.
Naloxone
Opioid overdose.
Short half-life compared to heroin. Monitor carefully.
Schizophrenia and Psychoses
Often associated with too much dopaminergic signalling.
Antipsychotic Drugs (neuroleptics)
1st Gen (typicals) -
Phenothiazines - chlorpromazine.
Thioxanthines - flupenthixol.
Butyrophenones - haloperidol
2nd Gen (atypicals)-
Clozapine
Risperidone
Chlorpromazine
A phenothiazine.
Low affinity for D2 receptors.
Antagonist of a-adrenoceptors, H1 histamine receptors, muscarinic ACh receptors.
Haloperidol
A butyrophenone.
Highest affinity for D2 receptor.
