1 Drugs Outline 2 Neurotransmitters Agonists and Antagonists Cocaine & other dopamine agonists Alcohol & its effects / Marijuana & its effects Synthetic & Designer Drugs: Ecstasy 1
Classes of Neurotransmitters 3 6 basic classes of NT: Peptides, Gases, Purines, Acetylcholine, Monoamines, and Amino Acids Neurotransmitters 4 Glutamate: general excitatory neurotransmitter GABA: general inhibitory neurotransmitter (Cl - ) Substance P: incoming pain signals Endorphins: pain management Serotonin (5-HT): sleep & mood Dopamine (DA): pleasure center & movement Norepinephrine (NE): sympathetic nervous system (induces aroused, heightened state) Acetylcholine (ACh): parasympathetic nervous system (induces calm, resting state) & motor system 2
Synthesis of NTs 5 Enzymes modify basic chemicals Synthesis of Catecholamines 6 Phenylalanine (dietary nutrient) PKU Phenylketonuria genetic deficit of enzyme to metabolize phenylalanine = mental retardation Metabolized to Tyrosine Enzymes modify: Tyrosine Dopa Dopa Dopamine Dopamine Norepinephrine Norepinephrine Epinephrine 3
Synaptic events 7 Outline 8 Neurotransmitters Agonists and Antagonists Cocaine & other dopamine agonists Alcohol & its effects / Marijuana & its effects Synthetic & Designer Drugs: Ecstasy 4
Agonists 9 A drug which stimulates the effects of a particular neurotransmitter or acts to enhance the transmitter s effect. Agonists 10 5
Antagonists 11 A drug which inhibits or counteracts the effects of a particular neurotransmitt er Drug Actions at the Synapse 12 6
Drugs working at Dopamine Synapse 13 Norepinephrine (NE) 14 Activates fight or flight resources Depression associated with norepinephrine depletion 7
Serotonin (5-HT) 15 Reuptake or monoamine oxidase deactivates Important in sleep regulation, depression, & mood disorders Gamma-aminobutyric Acid (GABA) 16 Main effect is to inhibit action of other neurons Lower levels associated with anxiety or panic attacks decreased levels in Huntington's disease 8
Outline 17 Neurotransmitters Agonists and Antagonists Cocaine & other dopamine agonists Alcohol & its effects / Marijuana & its effects Synthetic & Designer Drugs: Ecstasy Dopaminergic System 18 VTA ventral tegmental area Reward, motivation, planning Substantia Nigra Motor control Parkinson's disease associated with dopamine depletion Also associated with schizophrenia 9
Cocaine 19 Cocaine blocks the reuptake of dopamine Dopamine Build-up = pleasure feeling in the nucleus of accumbens & heightened arousal / alertness Cocaine blocks the recycling of dopamine everywhere in the CNS In the areas that control your breathing and heart rate dopamine increases activity resulting in heart attacks and loss of breathing control. Overstimulation can kill neurons. Excess dopamine can produce psychosis. Drug Video 20 http://www.youtube.com/watch?v=4os2c4nemji 10
Ritalin 21 Blocks DA uptake gradually Leads to increased concentration Outline 22 Neurotransmitters Agonists and Antagonists Cocaine & other dopamine agonists Alcohol & its effects / Marijuana & its effects Synthetic & Designer Drugs: Ecstasy 11
The Effects of Alcohol 23 Alcohol is very fat-soluble easy access through the blood-brain barrier interfere with the structure of the cell membrane & receptors in the membrane RESULT: inhibits Na + transport into all neurons The effects of alcohol seen in all systems - motor, vision, cognitive, etc. nonspecific to a NT The Effects of Alcohol 24 Alcohol impairs cognitive judgment so that people unintentionally hurt or kill themselves. Alcohol can reduce breathing and heart rate so much that the processes stop. Large amounts and chronic use of alcohol can damage neurons so that they die. 12
Outline 25 Neurotransmitters Agonists and Antagonists Cocaine & other dopamine agonists Alcohol & its effects / Marijuana & its effects Synthetic & Designer Drugs: Ecstasy THC Marijuana 26 Endogenous NTs for cannabinoid receptors: Anandamine: inhibits the pre-synaptic release of glutamate in hippocampal neurons ( LTP) inhibits the autonomic nervous system: relaxation, hypothermic, ocular pressure analgesic effects in the spinal cord 2-AG: inhibits LTP in hippocampus and suppresses pain sensations in the spinal cord 13
27 Cannabinoid Receptor Density Black labels CB receptors: high density in cerebellum, cortex, basal ganglion, & hippocampus Outline 28 Neurotransmitters Agonists and Antagonists Cocaine & other dopamine agonists Alcohol & its effects / Marijuana & its effects Synthetic & Designer Drugs: Ecstasy 14
What is Ecstasy? 29 Synthetic derivative of methamphetamine 30 Ecstasy - mimics both dopamine & serotonin neurotransmitters Ecstasy = artificial stimulation of dopamine and serotonin neurons to a higher degree than normal This over-stimulation can selectively kill the neurons that normally release dopamine & serotonin 15
Neurodegenerative Effects 31 Level of dysfunction Neurodegenerative Effects 32 Level of dysfunction 16
Drugs & Mechanisms of Action 33 DRUG: Behavioral: Mechanism: Amphetamine Cocaine Methylphenidate (Ritalin) Nicotine Alcohol Opiates Excitement, elevated mood Excitement, elevated mood Increased concentration Stimulant effects, tremors Relaxation, intoxication Relaxation, decrease pain Increased release of dopamine Blocks dopamine reuptake Blocks dopamine reuptake gradually Activates acetylocholine (ACh) receptor (neuromuscular synapses), increases dopamine in nucleus of accumbens Inhibits Na flux, activates GABA, inhibits dopamine Stimulates endorphin receptors Drugs & Mechanisms of Action 34 DRUG: Behavioral: Mechanism: Phencyclidine (PCP) Marijuana LSD Caffeine MDMA (ecstasy) Intoxication, hallucinations thought / memory disorders Intensified sensory, reduced pain, inhibit learning Distorted sensations Increased arousal Euphoria, hallucinations Inhibits NMDA-type glutamate receptors (found in specific areas in the temporal and occipital lobes) Activates anandamide receptors (hippocampus, basal ganglion, cerebellum) Stimulates serotonin receptors Vasoconstrictor, blocks adenosine (effectively increasing dopamine & ACh) Stimulates release of dopamine, activates serotonin receptors 17
For next time 35 Read Ch. 5 Study for Exam 1 18