Transcript Effects of drugs and other agents on the synapse

Effects of Drugs
and Other Agents
on the Synapse
Tada Obert
Department of Livestock & Wildlife
Management
Midlands State University
Contents
Stimulants
Sedatives
Anesthetics
Opiates/Opioids
Tranquilizers
Antidepressants
Psychedelics
 Marijuana/Mbanje
Stimulants
 most widely used are
 caffeine (in coffee, tea, and cola beverages)
 nicotine (in cigarettes)
 amphetamines
 cocaine
 these drugs mimic the stimulation provided by the sympathetic
nervous system.
 Nicotine binds to a subset of acetylcholine (ACh) receptors.
– nicotine is strongly addictive.
 Amphetamines and cocaine bind to — thus blocking — transporters
used for the reuptake of dopamine (and noradrenaline) into
presynaptic neurons.
– causes the level of dopamine to rise in the synapses & appear to
mediate the pleasurable effects.
Stimulants cont’d
 chief medical uses for amphetamines
 to help lose weight (becoz they suppress appetite);
 to help with Attention Deficit/Hyperactivity Disorder to perform
better in school.
 Cocaine
 been used for thousands of years in the Andes of South America.
 In order to achieve its effects, cocaine must cross the blood-brain
barrier.
 If antibodies are bound to the cocaine molecule, it cannot cross.
 this has raised the possibility of immunizing against cocaine (works
in mice).
Sedatives
 Sedatives induce sleep & include:
1. ethanol (beverage alcohol)
2. barbiturates, such as
 phenobarbital
 secobarbital (Seconal®)
3. meprobamate (Miltown®, Equanil®)
1. Ethanol/Ethyl alcohol
 the sense of well-being that it induces at low doses.
 perhaps low doses sedate those parts of the brain involved
with, for example, tension and anxiety and in this way
produce a sense of euphoria.
 however, higher doses depress brain centers involved in
such important functions as pain sensation, coordination,
and balance.
 at sufficiently high doses, the reticular formation can be
depressed enough to cause loss of consciousness.
2. Barbiturates
 often prescribed to prevent seizures as well as sleeping pills.
 mimic some of the action of alcohol
– particularly in their ability to depress the reticular formation (thus
promoting sleep) and,
– in high doses, the medulla oblongata (thus stopping breathing).
 barbiturates and ethanol both bind to GABAA receptors.
– ligand-gated channels that enhance the flow of chloride ions (Cl−)
into the postsynaptic neuron, thus increasing its resting potential
and making it less likely to fire.
 increase the natural inhibitory effect of GABA synapses.
3. Meprobamate
 prescribed as a tranquilizer, but its action is quite different from the
tranquilizers discussed below.
 molecular activity is like that of other sedatives and in combination
can produce a lethal overdose.
 sedatives produce two related physiological effects:
 tolerance — the necessity for a steadily-increasing dose to
achieve the same physiological and psychological effects
 physical dependence — withdrawal of the drug precipitates
unpleasant physical and psychological symptoms.
 These traits are also shared with nicotine, opiates, and other
psychoactive drugs.
Anesthetics
 Most of these are volatile hydrocarbons or ethers.
 They bind to GABA receptors in the spinal cord and brain decreasing
the sensitivity of the postsynaptic neurons.
 1,4-Butanediol is a common solvent.
– when ingested, it is converted into γ-hydroxybutyrate, an
increasingly-popular (and illegal) "club drug".
– γ-Hydroxybutyrate acts on GABAB receptors.
– Conversion of 1,4-butanediol to γ-hydroxybutyrate requires the
enzyme alcohol dehydrogenase, the same enzyme used to
metabolize ethanol.
– Ingesting both ethanol and 1,4-butanediol delays the effects of
the latter.
Opiates/Opioids
 substances isolated from the opium poppy or synthetic relatives.
 Examples:
 Morphine, codeine, heroin, methadone, oxycodone.
 depress nerve transmission in sensory pathways of the spinal cord and
brain that signal pain.
– explains why opiates are such effective pain killers.
 also inhibit brain centers controlling coughing, breathing, and
intestinal motility.
 morphine and codeine are used as pain killers.
– codeine is also used in cough medicine.
 are exceedingly addictive, quickly producing tolerance and
dependence.
 although heroin is even more effective as a painkiller than morphine
and codeine, it is so highly addictive that its use is illegal.
Opiates/Opioids cont’d
 Methadone is a synthetic opiate that is used to break addiction to
heroin (and replace it with addiction to methadone).
 Opiates bind to µ receptors of the G-protein located on the subsynaptic membrane of neurons involved in the transmission of pain
signals.
 Release of enkephalins suppresses the transmission of pain signals.
 By binding to enkephalin receptors, opiates like morphine enhance the
pain-killing effects of enkephalin neurons.
 µ receptors are also found on the cells in the medulla oblongata that
regulate breathing.
– accounts for the suppressive effect opiates have on breathing.
 Opiate antagonists
– such as naloxone (Narcan®) & naltrexone (ReVia®) bind to µ
receptors & prevent binding of opiates themselves.
Tranquilizers
 act like sedatives in reducing anxiety and tensions
– But do not have their sleep-inducing effect.
 often subdivided into the
 major tranquilizers and minor tranquilizers.
 Major tranquilizers
 Examples: Chloropromazine & haloperidol
 used to treat schizophrenia, a common and devastating mental
disease.
 act by binding to a class of receptors for the neurotransmitter
dopamine.
 drugs block the action of dopamine, and in a homeostatic response,
the neurons increase their activity.
 Minor tranquilizers (treat anxiety)
 most belong to a group called benzodiazepines, which act on
interneurons that use the inhibitory neurotransmitter GABA.
– bind to GABAA receptors on postsynaptic membrane & enhance
the action of GABA at the synapse.
Antidepressants
 increase the amount of serotonin at synapses that use it as a
neurotransmitter.
 Monoamine oxidase (MAO) inhibitors
– act on a mitochondrial enzyme that breaks down monoamines
such as noradrenaline and serotonin.
– by inhibiting the enzyme in presynaptic serotonin-releasing
neurons, more serotonin is deposited in the synapse.
 Tricyclics and tetracyclics
– block the reuptake of both noradrenaline and serotonin
causing an increase in the level of these neurotransmitters in the
synapse.
 antidepressants do not relieve the symptoms of depression until a
week or more after dosing begins.
– during this period, the number of serotonin receptors on the
postsynaptic membranes decreases.
 Bupropion blocks reuptake of noradrenaline and dopamine
 Atomoxetine selectively interferes with the reuptake of
noradrenaline
Psychedelics
 distort sensory perceptions, especially sight and sound.
 some e.g. mescaline, psilocybin and dimethyltryptamine
(DMT) are natural plant products.
 others are synthetic (lysergic acid diethylamide (LSD),
dimethoxymethylamphetamine (DOM),
methylenedioxymethamphetamine (MDMA or "ecstasy").
– DOM and MDMA share the stimulant qualities of amphetamines.
 all the psychedelics have a molecular structure that
resembles serotonin and probably bind to serotonin
receptors on the postsynaptic membrane.
Marijuana/Mbanje
 active ingredient in marijuana is delta-9-tetrahydrocannabinol
(Δ9-THC).
 binds to:
 CB1 receptors (G-protein-coupled receptors) that are
present on presynaptic membranes in several parts of the
brain;
 CB2 receptors that are found on cells of the immune system
(e.g., B cells and T cells).
 THC produces:
 the drowsiness of sedatives like alcohol
 the dulling of pain (like opiates) and
 in high doses, the perception-distorting effects of the
psychedelics.
Marijuana
 unlike sedatives and opiates, however, tolerance to THC does
not occur.
 drug is excreted so slowly from the body that, with repeated
use, a given response is achieved by a lower dose.
 turn out to have multiple effects, the clearest ones so far are
their effects on:
– appetite
• humans with cancer or AIDS find that marijuana
improves their appetite.
– neuronal activity in the brain.
• Marijuana has been used for centuries to control
epileptic seizures in humans.
KETE