How Do Drugs Affect the Nervous System Understanding
- Slides: 55
How Do Drugs Affect the Nervous System? …. Understanding Neural Transmission Drugs act on Neurons and their communication with other cells
Beauty in the nervous system?
The Basis of the Nervous System • Neurons – Single cell unit of the nervous system – 10 billion in the brain alone – Receives, processes and transmits information • Each neuron in the brain received signals from thousands of other neurons.
In most respects the neuron is like other cells of our body
But is different in that it can produce electrical impulses near its cell body region
A Classical Study showing the RESTING MEMBRANE POTENTIAL (RMP) of the Neuron
The RMP • The RMP for a typical neuron is about -70 mv
“Threshold” voltage change (depolarization) triggers the “Action Potential” Hyperpolarizationin the case of neurons means to make the RMP more negative. Depolarization means to make the RMP more positive Threshold level of depolarization Triggers an ACTION Pot.
Once triggered, the AP is all or none, and “one-way. ” The AP will travel to the terminal and there initiate a chemical event
The Neuronal communication process can be thought of as an “electro-chemical” event. Most Psychoactive drugs directly affect the chemical portion of the process
Action Potential at the Terminals
Terminal Boutons end adjacent to other cells… The Synapsea very small space between the boutons of one neuron and typically the dendrites of another.
The Synapse: PRESYNAPTIC and POSTSYNAPTIC processes Any process associated with the terminal bouton of Neuron “A” are considered to be presynaptic processes. Any process associated with effects of NT release on neuron “B” are considered postsynaptic processes.
PRESYNAPTIC Exocytosis The Action Potential leads to release of Neurotransmitter substance (exocytosis) into the synapse.
Synaptic release of Neurotransmitter substances may in turn affect “postsynaptic” neurons
Neurotransmitters There are many different Neurotransmitter Families. Different NTs are found in different pathways and are involved in different functions/ or different components of functions.
Some Classical NTs, terminology and postsynaptic effects NTs Terminology Acetylcholine/ACH Serotonin/5 -HT Cholinergic serotonergic +/+/- GABA-ergic - (gamma-amino-butyric acid) Glutamate/Glu Glutamatergic Norpinephrine /NEAdrenergic Dopamine /DA Dopaminergic Enkephalin/Endorphin Post synaptic effects + +/+/+/-
Some Basic Functions Associated with Different NT Families: • Acetylcholine-(ACH, cholinergic) -Skeletal Muscle control -Parasympathetic Autonomic functions -Thirst -Memory: Alzheimer’s disease
Pattern of projection pathways associated with acetylcholine brain nuclei ( cholinergic systems
Norepinephrine- (NE, noradrenergic, a catecholamine) – Sympathetic ANS functions – hunger – mood
Noradrenergic system (Norepinephrine)
Dopamine- ( DA, dopaminergic, a catecholamine) – movement (Parkinson’s disease) – “wanting” – mood –attention, and learning. –Dopamine excess may be involved in Schizophrenia.
Dopamine
Parkinson’s Disease • Parkinson’s disease, dopamine and the substantia nigra
Parkinson’s disease and MPTP • 1980’s “designer drugs” MPPP/MPTPP and the case of the frozen addicts •
Serotonin ( 5 -HT, serotonergic, an indolamine) • -sleep, dreaming, mood
Serotonergic System (Serotonin)
Endorphins • Modulate the experience of pain • Involved in breathing and heart rate, cough reflex, nausea and vomiting • Involved in feelings of euphoria and reward
GABA • Most prevalent inhibitory neurotransmitter in the brain • GABA secreted by “local” interneurons all over the brain. • Implicated in relaxation/anti-anxiety
Glutamate • Most prevalent excitatory NT. • Involved in many brain circuits, but especially important in the formation of memories. • Brain injury is associated with release of Glut. In high concentration, which in turn may be toxic to neurons.
Neurotransmitters bind to receptor sites to produce postsynaptic effects
NT-Receptor Specificity A given NT substance will only activate specific receptor proteins, and can not activate receptors for other NTs l l l Lock & Key Model NT = key Receptor = lock Activation of a receptor will lead to either Excitation or Inhibition.
How can one NT sometimes produce excitatory postsynaptic effects and in other cases produce inhibitory postsynaptic effects? NTs Terminology Acetylcholine/ACH Serotonin/5 -HT Cholinergic serotonergic +/+/- GABA-ergic - (gamma-amino-butyric acid) Glutamate/Glu Glutamatergic Norpinephrine /NEAdrenergic Dopamine /DA Dopaminergic Enkephalin/Endorphin Post synaptic effects + +/+/+/-
One Neurotransmitter may activate any of a “family” of receptor subtypes ACH in the ANS can activate the “Muscarinic” ACH receptor (m. ACH), a metabotropic receptor type. Activation of the m. ACHr leads to an inhibitory response. ACH release in the somatic branch of the PNS activates the “Nicotinic” ACH receptor (n. ACHr). An ionotropic receptor type. Activation of the n. ACHr leads to an excitatory response.
Effects depend on receptor subtype
Deactivation of NT’s • Enzyme Breakdown • Reuptake
NT-receptor interactions must stop! Enzymatic degradation ACH is broken apart in the synapse by the enzyme acetylcholine-esterase (ACHE). The importance of the termination of NT-receptor interactions is critical for normal function…. .
“Nerve Gases” – and their typical mechanism of action…
Most nerve gases produce their effects by blocking the breakdown of ACH ( by binding to and blocking the action of ACHE).
The blockade of ACHE leads to too much ACH in ACH synapses, and exaggerated postsynaptic effects. Effects of Nerve gas exposure Neuromuscular Effects • Twitching • Weakness • Paralysis • Respiratory failure Autonomic Nervous System Effects • Reduced Vision • Small pupil size • Drooling • Sweating • Diarrhea • Nausea • Abdominal pain • Vomiting Central Nervous System Effects • Headache • Convulsions • Coma • Respiratory arrest • Confusion • Slurred speech • Depression • Respiratory depression
Monoamine Oxidase: MAO • MAO acts to break down NE and 5 -HT
Reuptake The serotonin transporter enzyme is responsible for terminating the effects of 5 -HT in serotonergic synapses
Of Interest? ? ? Selective serotonin reuptake inhibitors. Bind to and reduce the effectiveness of the 5 -HT transporter SSRIs approved to treat depression, with their generic, or chemical, names followed by available brand names in parentheses: Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac, Prozac Weekly) Paroxetine (Paxil, Paxil CR, Pexeva) Sertraline (Zoloft) These medications may also be used to treat conditions other than depression. Side effects of SSRIs All SSRIs have the same general mechanism of action and side effects. However, individual SSRIs have some different pharmacological characteristics. That means you may respond differently to certain SSRIs or have different side effects with different SSRIs.
Of interest? ? SSRI possible side-effects Side effects of SSRIs include: Nausea Sexual dysfunction, including reduced desire or orgasm difficulties Dry mouth Headache Diarrhea Nervousness Rash Agitation Restlessness Increased sweating Weight gain Drowsiness Insomnia
How Do Drugs affect the nervous system? Ligand – a fancy term for substances that bind to receptors -neurotransmitters -drugs
In general we classify drug effects into 2 basic types: Drugs may act as Agoniststhe Ligand may mimic the NT and activate the receptor, or facilitate the natural effects of the NT in indirect ways • Drugs may act as Antagonists: • The ligand may block the receptor, or in indirect ways decrease the effect of the NT at its receptor.
Drug Action • Direct Agonist: Ligand Activates receptor • Direct Antagonist: Ligand Blocks receptor • Indirect agonism or antagonism • Alters enzyme activity • Blocks reuptake • Etc…
Forms of Drug Action at the Synapse • Ways to agonize – – – Stimulate release Receptor binding Inhibition of reuptake Inhibition of deactivation Promote synthesis 8. Autoreceptors • Ways antagonize – Block release – Receptor blocker – Prevent synthesis
Acetylcholine Agonists Nicotine Physostigmine Antagonists Muscarinic receptor Atropine Nicotinic receptor Curare
Dopamine • Cocaine – dopamine reuptake inhibitor • Amphetamine – increases DA release • Antipsychotics – block post-synaptic dopamine receptor
Cocaine acts as a monoamine agonist by blocking the reuptake transporter enzyme
Serotonin • Selective-serotonin reuptake inhibitors (SSRIs) – used to treat depression
GABA • Valium, Xanax, Ativan • Act as GABA agonists • GHB, Rohypnol • GABA agonist
- Neuronal pool
- Nervous
- Processes of a neuron
- Section 35-1 human body systems answer key
- Drugs that affect basic driving skills are
- Nervous system and digestive system
- Endocrine system and nervous system
- Mechanism of hormone action
- Endocrine system
- Chemical messengers of the nervous system
- Segmentation of nematoda
- The nervous system is made up of
- Primary functions of the nervous system
- Nervous system learning objectives
- Bipolar neuron function
- What is stimuli in nervous system
- Spinal cord structure
- Adrenal gland sympathetic nervous system
- Autonomic nervous system def
- Spinal cord 31 pairs
- Sns somatic nervous system
- The nervous system brain scienstructable
- Skeletal muscle autonomic nervous system
- Nematoda
- Arthropoda insecta
- Jointed foot
- Are arthropods coelomates
- Major divisions
- Parasympathatic nervous system
- Nervous system in coelenterata
- Autonomic nervous system consists of
- Differences between nervous system and endocrine
- Ans
- Brain layer
- Basic unit of nervous system
- Blood clotting positive feedback diagram
- Cns histology ppt
- White matter
- Comparison of endocrine and nervous system
- 8 divisions of the nervous system
- How to take care of your nervous system
- Nervous system effector cells
- Chapter 15 nervous system diseases and disorders
- Are endocrine glands ductless
- Beta-blockers for overactive sympathetic nervous system
- Ciliary ganglion
- Spinal cord dorsal and ventral roots
- Excretory system of silkworm
- 35-3 divisions of the nervous system
- What is the building block of the nervous system
- Structure of nervous system graphic organizer
- Medunerve
- Classification of planaria
- 2 forms of cnidarians
- Ventral root and dorsal root
- Sympathetic and parasympathetic nervous system difference