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Nervous System (CENTRAL NERVOUS SYSTEM BIOLOGY (SEROTONIN (5…

- - - - CENTRAL NERVOUS SYSTEM
      - GASTRO-INTESTINAL TRACT FROM TRYPTOPHAN FROM enterochromaffin cells
        
        PRECURSOR TO TRYPTOPHAN IS TRYTOPHAN HYROXYLASE
        
        TRYPTOPHAN HYDROXYLASE IS NOT SATURATED
        
        dietary levels of
        tryptophan can effect serotonin production
        
        AGENTS INHIBITING 5-HT reuptake
        
        cocaine
        
        TCA’s
        
        SSRI’s
    - - OCD
      - PTSD
      - panic disorder
      - autism
    - - Functional polymorphisms of 5HT transporter genes
        
        associated with depression
        
        Asscociated with autism
    - - PROLONGED PERSISTENT STRESS - ACTIVATES THE HPA AXIS
        
        subsequent hyper-secretion of ACTH and cortisol
        
        alter
        chaperone proteins which are essential for maintaining serotonin
        receptor integrity
        
        thIs leads to a low serotonin state
    - - Serotonin (5-HT) IS AN IMPORTANT SIGNALLING MOLECULE IN THE GUT
      - intrinsic reflexes
        
        stimulation of
        motility patterns
        
        epithelial secretion
        
        vasodilation
      - Activation of extrinsic
        vagal and spinal afferent fibres
        
        results in slowed gastric emptying,
        
        pancreatic secretion
        
        satiation,
        
        pain and discomfort,
        
        nausea and
        vomiting
        
        may play an important role in irritable bowel syndrome, and functional
        constipation
    - - suicide
      - violent crimes
      - hostility
      - insomnia, depression
      - impulsive acts with no concern for punishment
      - alcohol abuse
      - reckless driving
        • substance abuse/addictions
      - eating disorders
        • exhibitionism
      - argumentative behaviour towards family and friends
        • obsessive compulsive disorders (OCD)
        • irritable bowel syndrome (IBS)
    - - Psychiatric medications
        
        MAOI’s
        
        TCA’s
        
        SSRI’s
      - Serotonin syndrome can result if too high levels of Serotonin are produced
        
        potentially fatal complication to treatment
        with serotonin reuptake inhibitors
        
        Most commonly associated with the concurrent use of two or more
        drugs that enhance serotonin neurotransmission
        
        EARLY SYMPTOMS
        
        muscle cramps
        
        stiffness or tics
        
        waking feeling hung-over
        
        SEVERE SYMPTOMS
        
        confusion
        
        agitation and restlessness
        
        CONCURRENT USE OF ANY SEROTONIN PRODUCING NEUTRACEUTICAL OR HERBAL SHOULD BE AVOIDED!!
        
        shivering
        
        ataxia
        
        fever
        
        diaphoresis
        
        hypertension
        
        tachycardia
      - Tryptophan rich diets increase the saturation of tryptophan hydroxylase
        
        Serotonin precursors
        
        5-Hydroxytryptophan (5-HTP) from Griffonia simplicifolia
        
        Tryptophan
        
        Hypericum perforatum increases levels of serotonin
  - - - cytokines
        
        blood and urine testing for these and their breakdown
        metabolites can be inaccurate due to the fact that they will often
        show peripheral instead of central nervous system activity
      - peptides
      - nitric oxide
      - neurotrophic factors
    - - Excitory AP
      - Inhibitory AP
    - - these work either directly or through a secondary
        messenger system
      - Termination of activity is rapid
      - NT is pumped back to the presynaptic terminal
      - reuptake, or
        destroyed by enzymes
    - - Synthesis of NT
      - Storage
      - Release
      - Degradation
      - Changes in number of NT
      - Affinity of receptors
- - - - 5-HTP is then CONVERTED TO SEROTONIN (5-
        hydroxytryptamine)
      - 5-HYDROXYTRYPTOPHAN (5-HTP)
        
        PRECURSOR TO SEROTONIN
        
        SUGGESTED AS A THERAPY FOR MANY CONDITIONS
        
        cerebellar ataxia
        
        headache,
        depression
        
        psychiatric disorders
        
        fibromyalgia
        
        appetite suppressant
        or weight-loss agent
        
        SIDE EFFECTS
        
        gastrointestinal disturbances
        
        mood disturbances
        
        seizure
        
        abnormal blood counts
        
        CONTRAINDICATIONS
        
        gastrointestinal disorders
        
        Use cautiously in patients taking antidepressant medications
        
        DOSING
        
        Cerebellar ataxia: 10-16mg/kg daily has been used
        
        Depression: 200-300mg daily has been used
        
        Fibromyalgia: 100mg three times daily has been recommended
        
        Headache: 300-600mg daily orally in divided doses has been used
        
        Obesity: 8mg/kg daily or 750-900mg daily has been used
        
        Psychiatric disorders: 25-350mg daily has been used for anxiety
        
        Sleep disorders: Oral loading with 5-HTP has been used to treat the REM fragmentation in a group of
        alcoholics who were abstinent following acute ethanol withdrawal
        
        Seizures/epilepsy (myoclonic disorders): Several clinical studies have used 5-HTP (15mg/kg daily) in
        combination with carbidopa for 14 days to one month, although results indicated no clinical improvement
    - - – red meat
      - dairy products
      - nuts,
      - seeds
      - bananas
      - soybeans and soy
        products
      - tuna, shellfish
      - turkey
  - - - BOTH L-TRYPTOPHAN AND 5-HTP CAN PENETRATE THE BBB
  - - - can cause a relapse in treated
        depression
      - precipitate depressive symptoms in patients with a
        history or family history of depression
      - Can cause depression in healthy
        volunteers
      - bulimia relapse,
      - deterioration of schizophrenia symptoms
- - - - catechins
- - - - naphthodianthrones
        
        hypericin
        
        pseudohypericin
      - phloroglucinols
        
        hyperforin
        
        adhyperforin
  - - - Inhibit monoamine oxidase (MAO)