all these drugs alter the transport of ions = altering the conentration of chemicals (neurotransmitters) at synapses

one exception: antiseizure drugs act by altering membrane potentials along axon

- restricts entery of drugs into the CNS

- due to tight junctions between endothelial cells in the capillaries in the brain

- no such thing in peripheral nervous system

1) lipophilic drugs

2) transport into the CNS via transporters that are normally for nutrients

3) inflammation of the meninges or the brain

-70 mv

kept by the Na-K ATPase (Na pumped out, K in)

Cl also going out

PROPIGATION OF THE ACTION POTENTIAL

Sodium rushes in through voltage-gated Na channels (these channels are present on nerve and muscle cells) - open in response to depolarization to further depolarize (or repolarize) the membrane

anatomically well defined systems, in particular the sensory and motor systems

generally utilize amino acids as neurotransmitters

anatomically less well-defined

tend to be implicated in global functions

utilize monoamines and peptides as neurotransmitters

1) Norepinephrine

2) Dopamine

3) Serotonin (5-HT neurons)

cell bodies found in:

1) Pons (locus ceruleus)

2) Midbrain

Project diffusely to virtually all regions of the crebral cortex and limbic system

regulates arousal and mood

1) anatomically more limited than noradrenergic neurons

2) extrapyramidal motor control (site of action of antiparkinson drugs)

3) limibic system (site of action of antipsychotic drugs)

4) hypothalamic-pituitary axis

five receptor subtypes

fall into D1 or D2 family

D1 - Agonist = none in use

- Antagonist= phenothiazines

D2 - Agonist = bromocriptine

-Antagonist=phenothiazines

1) Nigrostriatal - extrapyramidal motor control

- important for movement disorders (parkinson's, Frozen Man Syndrome)

2) Tuberoinfundibular (neuroendocrine regulation)

3) Mesolimbic (emotions, reward system)

1) Nigrostriatal Pathway = Parkinson's (selective cell death), MPTP Frozen Man syndrome (toxin transported into neurons)

2) Substantia nigra to limbic system and widespread cortex = addiction and behavioral disorders

3) Arcuate nucleus of hypothalamus to anterior pituitary (via portal veins): inhibits prolactin secretion

most cell bodies = in midline region of the pons;

project diffusely to most of the CNS (ascend to the cerebral cortex and limbic system from the midline tegmentum (raphe nucleus)

-regulating emotions

- sleep-wake cycles

-temperature control

Antipsychotics and antidepressants

1) mood disorders (SSRIs improve depression)

2) migrane pain

3) chemotherapy-induced emesis (ondasetron 5-HT3 antagonist)

4) LSD activates 5-HT1 and 2 receptors

both long and short cholinergic pathways are present at all levels of the CNS, particularly cerebral cortex and limbic system

most CNS effects are mediated by a large family of muscarinic receptors (slow excitation)

implicated in cognitive function (esp. MEMORY)

action is terminated by cholinesterase

Answer: M₁ type - they slowly open the rectifying potassium channel causing slow excitation

(Nicotinic and M₂ receptors are present, but in much lower density)

1) Motor neurons in spinal cord to the NMJ - acetylcholinesterases (nerve gases), insecticides; myasthenia gravis; botulism

2) basal forebrain to cortex - Alzheimer's disease (selective cell death/atrophy = cognitive defects --> tacrine, donepizil, galantamine, rivastigmine are CE inhibitors used for Alzheimer's tx);

autosomal dominant frontal lobe epilepsy (mutations in CNS ACh receptor)

3) Atrophy of neurons in extrappyramidal system is thought to contribute to the tremor in Parkinson's

amino acid NT

cell bodies found primarily in the spinal cord

INHIBITS NEURAL ACTIVITY

Strychnine (poison) antagonizes glycine inhibition by blocking the glycine receptor --> convulsions

mediates inhibitory actions of local interneurons

found in: - cerebellum

-cerebral cortex

-limbic system

two receptor subtypes: GABA-A, GABA-B

1) Major inhibitory NT in brain: sedative - hypnotic drugs act by facilitating the action of GABA

barbituates in high does can directly activate the GABA receptor -- profound respiratory depression and CV collapse

2) Epilepsy - gabapentin and valproic acid increase GABA

widely distributed in the CNS,

generally excitatory

two major classes of receptors: NMDA and non-NMDA

NMDA: blocked by ketamine, PCP; activated by a new class of antipsychotics

1) tranquilizing/anesthetic agents - ketamine and phencyclidine; act by blocking the NMDA receptor --> disordered thinking similar to schizophrenia

2) antiphyschotic drugs in develoment are NMDA agonists

these proteins are cleavage products of a larger peptide (pro-opiomelanocortin)

are part of endorphin/enkephalin families --> variety of receptors; generally inhibitory

endogenous ligands for the opioid receptors

167 amino acid long - secreted only by adipose tissue (not strictly a NT)

its receptors are found in the CNS

obese individuals have INCREASED levels

binds to ventromedial hypothalamus to induce satiety and increase lipogenesis (obesity = leptin insensitivity)

Present in gut and endocrine tissues and in CNS:

• vasoactive intestinal peptide (VIP)
• cholecystokinin (CCK)
• thryotropin releasing hormone (TRH)
• somatostatin

Substance P = transmission of pain

endocannabinoids

Receptor = CB1 = is widely distributed in the CNS -- are primarily presynaptic

endogenous ligands are thought to be brain lipids (which is different from other NTs because these are NOT STORED. Instead, they are synthesized in response to stimuli and act in a retrograde fashion)

secreted from the postsynaptic neuron and bind on CB1 on presynaptic neuron --> inhibit neurotransmitter release

Activation of these receptors affects: memory, cognition, and pain perception