Small Molecule NTs Cholinergic Catechols Biogenic amines Indole Imidazole AA - Excitory AA- Inhibitory Adenine NT

Neurotransmitter Acetylcholine Dopamine Norepinephrine Epinephrine (adrenergic) Serotonin Histamine Glutamate Aspartate GABA Glycine Purine/Adenosine

Precursor(s) Acetly CoA and Choline Tyrosine --> L-Dopa Dopamine Norepinephrine Tryptophan --> 5-hydroxytryptophan --> Histidine Glutamine Glutamate (vice-versa) Glutamate serine

Large Molecule NTs Opiates

Methionine enkephalin endorphins

proopiomelanocortin (POMC) proopiomelanocortin (POMC)

Substance P Somatostain-14 Thyrotropin releasing hormone (TRH) Cholecystikinin (CCK) Vasoactive intestinal p. (VIP) Leutinizing h. releasing h. (LHRH) Oxytocin

Enzyme/Location Vesicular transport Receptor choline acetyltransferase (CHAT) transporter Transmitter-gated Ion Channel vesic. Ach Tyrosine hydroxylase --> aromatic aa decarbxylase Dopamine hydroxylase/NE vesicle vesicular monoamine transporter Phenylethanol-amine N-methyl-transferase Tryptophan-5-hydroxylase --> aromatic aa decarbxylase Transmitter-gated Ion Channel Histidine decarboxylase Glutaminase/mitochondria VGLUT Transmitter-gated Ion Channel glutamic acid decarboxylase (GAD) serine transhydroxymethylase ATPase/ECS Transmitter-gated Ion Channel Transmitter-gated Ion Channel Transmitter-gated Ion Channel Degrading Enzyme/Speed acetylcholinesterase (synpase)/fast reuptake. Monoamine oxidase(pre-syn) Glu synthetase (glial cells)/fast G-Protein Coupled . Monoamine oxidase(pre-syn) Cateo reuptake.

SNS. CNS Substantia nigra and ventral tegmental area (midbrain) throughout cortex and striatal complex (hippo) Locus coeruleus (midbrain) throughout cortex.Location Projections NMJ. hippocampus. cerebellum raphe nucleus (midbrain) and and subcortical features cortical brainstem Tuberomammillary nucelus ofregions cortical hypothalamus Brain. ENS. PNS. Spinal cord spinal cord CNS CNS CNS CNS . Spinal cord Brain.

tx resistant depression MAOI . enuresis. Zyban) NE and DA Reuptake Blocker Mirtazapine (Remeron) Nefazodone (Serzone) NaSSA SARI Trazodone (Desyrel) SARI Class Indications atypical depression. OCS (clompramine only).second line Uticaria. Tricyclic Antidepressants . bulimia. Panic disorder.second line MDD. pruritis . dysthmia. MDD. Pain (Migraine.ANTIDEPRESSANTS Mechanism Iproniazid Phenelzine (Nardil) Tranylcypromine (Parnate) isocarboxazid (Marplan) Selegeline (Emsam) Impramine Clomipramine Norptriptyline Fluoxetine (Prozac/Serafem) Paroxetine (paxil) Sertraline (Zoloft) Fluvoxamine (Luvox) Citalopram (Celexa) Escitalopram (Lexapro) MAO-A inhibitor MAO-A/B inhibitor MAO-A/B inhibitor MAO-A/B inhibitor MAO-A/B inhibitor Tricyclic AntiD Tricyclic (OCD only) Tricyclic AntiD SSRI SSRI SSRI SSRI SSRI SSRI Buproprion (Wellbutrin. panic disorder. chronic pain).

sedation or weight gain can be useful) esp in elderly) Depression. Pain SNRI (5HT-NE reuptake inhib) NDRI (NE and DA reuptake Inhib) NRI (NE reuptake Inhib) Depression. Anxiety. Generalized anxiety disorder. bulimia nervosa.5HT2C . no nausea .5HT2A . Dysthymia. anti-depressant anxiolytic. drowsiness dizziness. Panic Disorder. Social Anxiety Disorder. anxiety. weight gain no GI problems. decreased BP anxiolytic. Insomnia acts like MAOI for all 3 nts! target glucocorticoid sys abortion pill NaSSA (Noradrenergic and specific 5HT Antidepressant) SARIs (5HT Antagonist and Reuptake Inhib) SDNRIs (triple reuptake inhib) Substance P antagonists CRF antagonists RU486 anti-histamine anticholinergic anti-alpha adrenergic Serotonin Receptors . panic disorder. blurred vision. dry mouth. no sexual dysfunction anxiolytic. premature ejaculation. pre-menstrual dysphoric disorder. ADHD Major depression. sleep restoring. ADHD Depression (in EU). OCD.5HT1A . Smoking cessation. Generalized Anxiety Disorder. PTSD. dysthymia. Diabetic Neuropathy.SSRI MDD. minor depressoin. insomnia. pain syndrome Depression.5HT3 Effects of antogonism: weight gain constipation.

Pros No anticholinergic sideeffects significant overdose potential. Orthostatic No weight gain. rare fatal hepatotoxicity Side Effects HT crisis (lethal. mild sedatoin. and anti-cholinergic . orthostatic HT.Result Side Effect More NE in the pres-synN --> more NE in the cleft NE and 5HT reuptake transporter inhibition-> more NE and 5HT in cleft 5HT reuptake inhibitor NE and DA reuptake pump inhibitor --> inc NE and DA in synapse anti-alpha-2 blockade --> inc both 5HT and noradrenergic transmission (esp at 5HT1A) 5HT2A blockade inc 5HT to therapeutic Sedation. anti-alpha1. requires tyraminerestriction). sexual dysfunction. weight gain. also has anti-histamine. cardiovascular toxicity. no sex dysfunction.

antidepression. no nausea. weight gain (2C. Discontinuation Sydrome (when SSRI stopped appruptly. diarrhea. 2C and 3 blockade: anxiolytic. hyperpyrexia. diarrhea). delerium. 2A). death). Avoid: daily dose >450mg. tachycardia. myoclonus. HT. sexual dysfunction. Sexual dysfunction (esp. sedation (H1. better tolerated 5HT side effects: GI. NE side effects: Tremor agitation.5HT side effects (GI. HT. clinical indicators for seizure. weight gain. fatigue). anorgasmia). dry mouth. agitation. No NE uptake inhibition and anti-histamine. myoclonus. headaches. dizziness. sweating. wide therapeutic index. no GI issues. so no sexual dysfunction or weight gain antihistaminergic effects. drowsiness oring. nausea. 5HT syndrome ( diarrhea. in appetite). sleep restoring vision. sustained HT Increased seizure risk (esp bulemics). irritability. history of eating disorders Tremor. akathesialinked?). fever. (see specific 5HT receptor effects) due to 5HT-2A. vomitting. activation. Suicidality (mania. real inc. and anti-cholinergic action. Tachycardia Little or no 5HT action. no sexual dysfunction . nausea. anti-alpha1. vomitting.

many OTC cold medications.Drug Interactions Narcotics (Merperidone/Demerol). Antidepressants (Tricyclic and SSRI). .

.

MAO A MAO B NE and serotonin dopamine .

glutamatergic excitation . thereby boosting GABA inhibition and decr.Gabapentin (Neurontin). somewhat safer) Inhibition of Na/K channels. thereby boosting GABA inhibition and decr. glutamatergic excitation .Valproic Acid (Depakote/Depakene) Inhibition of Na/Ca channels. omega 3 fatty acids.typical and atypical antipsychotics.Lamotrigine . inhibits Na and glutamate .Drug/Class Mechanism Lithium Anticonvulsants modulates phosphatidyl inositol second messenger system .Carbamazepine (Tegretol)/ Oxcarbazapine (Trileptal. Ca channel blockers. benzodiazepines unclear. Topiramate (Topamax) Other Bipolar Agents .

bipolar maintenance. pure bipolar depression. edema. dizziness. sedation. hepatotoxicity. diarrhea. cog dulling. Teratogenicity (nerual tube defects. rapid cycling. tremor. sedation. nephrotoxicity. neurotoxicity (cog blunting & ataxia). 2nd line: mized mania. decr creativity. vomiting. suicide prevention thrombocytopenia. cardica arrhythmias. dizziness. aplastic anemia). Dyspepsia and diahhrea.Indications Toxicities Hypothyroidism. overdose. lightheadedness. anticholinergic effects. hepatoxicity. overdose. agranulocytosis. Nausea. line: pure depressive states. 1% Steven Johnson Syndrome. 1st line: mized (dysphoric) mania. GI: abdominal cramps. inc appetie and weight gain. polycystic ovarian syndrome. acne. sedation. rash. weight gain bipolar disorder (mixed mania. anorexia. diarrhea. 2nd tremor. decr memory and concentration. inc thirst and urination. teratogenicity. pancreatitis. cog blunting. craniofacial abnormalities). Metabolic: weight gain. generally less serious. Derm: psoriasis. allergic reactions. classic euphoric mania hair loss Hematologic side effects (thrombocytopenia. overdose. tremor. nausea. nausea. rapid cycling. renal polyuria and polydipsia (nephrogenic diabetes insipidus). vomiting. electrolyte abnormalities. 10% rash. rapid cycling) softer' bipolar disorders . Neuro: cognitive dulling. vomiting. benign leukocytosis 1st line: classic euphoria mania. teratogenicity (neural tube defects).

Thiazide diuretics.Drug Interactions NSAIDs. including itself . Ca channel blockers Induces Cyt p450 system. ACEi. causes decr levels of many other medications.

Diazepam (Valium) .Lorazepam Ativan). Oxazepam (Serax).TCAs Anticonvulsants Antihistamines Atypical Antipsychotics Barbituates GABA-ergic.Mirtazapine .BZ-1 (Omega 1) . allosteric binging to GABAR --> inc frequency of opening upon GABA binding --> leading to enhanced Cl. req 2-3 weeks for effect Buspirone .flow into cell (hyperpolarization).SSRI .BZ-3 work on BZ receptor but not BZ selective BZ-1 agonist selective BZ-1 agonist selective BZ-1 agonist 5HT 1A receptor agonist that cuases upregulation of autoreceptors on pre/postsynaptic neuron.Clonazepam (klonopin) . MAOIs Atypical Antipsychotics Beta-Blockers Anticonvulsants Antihistamines INSOMNIA Drugs Antidepresants .ANXIETY DISORDERS Drug Antidepresants . Temazepam (Restoril) Glucoronidated BZs.Mirtazapine .Nefazodone . work in 1-2 weeks high potency/long half-life high potency/short half-life Benzodiazepines .Alprazolam (Xanax) .BZ-2 . allosteric binging to GABAR --> inc duration of opening upon GABA binding --> leading to enhanced Cl.Venlafaxine .TCAs. avoid Phase 1 metab (liver oxidation) and get glucoronidated and excreted through the liver --> no liver-metabolism Hypnotics/Sedative BZs Benzodiazepine Receptor Agonists .flow into cell (hyperpolarization) GABA-ergic.Trazodone .

pituitary and retina to increase melatonin secretion that is implicated in drowsiness .Ramelteon Melatonin Receptor agonist. binds receptors in the hypothalamus.

overdose (Jimmi Hendrix and Marilyn Monroe!) Anxiolytic (short vs long-term) for GAD. ataxia. other anxiety disorders? Augmentation dizziness. dependance. Panic Disorder. paradoxical disinhibition. abuse potential insomnia anxiolysis and sleep muscle relaxant unsure GAD. nausea. adjustment disorder. alcohol withdrawl combination with alcohol is dangerous rapid discontinuation leads to problems.2nd line depressed all levels of CNS. OCD. muscle relaxant. dec respiratory drive. anticonvulsant. headaches. sedation. tolerance. narrow therapuetic index. respiratory depress. insomnia. for depression tx? contraindicated with MAOI . nonpathologic anxiety. cog effects. drowsiness.

more subtle effect .

no abuse potential. withdrawl and seizures non-sedating. less overdose. alcohol tolerant more specific. no respiratory or cardiac effects. less lethal overdose. broader therapeutic index. addiction.BZ on it's own will not cause Cl to flow!! safer and more efficacious than barbituates. few drug interactions . tolerance or withdrawl.

etc .no risk of addiction. tolerance.

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