09/04/2009 00:39:00

← 3/10/09
← GluRs – Metabotropic glutamate receptors: mGluRs
← L-glutamine
↓ (via glutaminase)
← L-glutamate (mitochondrial)
← 
← α-ketoglutarate (mitochondrial)
← 
← dicarboxylate carrier outside of mitochondria

α-ketoglutarate (cytoplasmic)

L-glutamate via AA (cytoplasmic)
 GS or GAD  (in glia)
L-glutamine GABA (inhibitory neurons)

← Na+- dependent:
 Excitatory Amino Acid Carrier-1 (EAAC-1)
 Glu Transporter-1 (GLT-1)
 Glu Aspartate Transporter (GLAST)
← H+ and Mg2+ dependent:
 Vesicular ATP-ase Glutamate Transporter (VGlu-T)
← Na+ and H+ dependent:
  Glutamine Transporter (Gln-T)
←
← Current structural model of mGluRs – Homodimers
 Regional expression varies: mGluR1, 5, 6 – due to experience!!
 Class I
o mGluR1 and mGluR5
o  IP3 and Ca2+
 Class II
o mGluR2 and mGluR3
o  cAMP
 Class III
o mGluR4 and mGluR6-8
o  cAMP
←
← mGluR Functional Attributes
 Involved in:
o perception of pain
o mood/affect, especially anxiety
o learning and/or memory
o blood flow / headache
 Modulation of the activity of:
o Voltage-dependent ion channels
o Transmitter release
o Ca2+-dependent ion channels (K+)
 o Ligand-gated ion channels
←
← Group I Effecter Mechanisms
← Glu

← 
← mGluR1/mGluR5
← 
← Gq
← 
← PLC & PIP2
← 
← IP3 + DAG
←  
Ip3R PKC
AGO (competitive)
 Glu endogenous
 Ibotenate
 DHPG (3,5-dihydroxyphenylglycine)
← ANT (competitive)
 CPG (carboxyphenylglycine; especially 4-CPG)
← Group I agonist can increase excitability
 There is no AHP after DHPG is added; spike-frequency accommodation blocked
and easily excited
 But both pre and postsynaptic effects are observed
 cause headaches & reduce transmitter release by reducing Ca2+ influx
← Group II, III Effector mechanism
← Glu
← 
Group II, III
← 
Gi
← 
AC 

cAMP 

← PKA 

← Group II
 AGO
o Glu
o NAAG (N-acetylaspartylglutamate)
 ANT
o EthGlu (ethylGlu)
← Group III
 AGO
o Glu
o AP4
 ANT
 o MAP4
←
←
←
←
←
←
←
←
←
←
←
← GABABRs II
← GABA biosynthesis and metabolism
← Glu
←  (GAD)
← GABA
←  (GABA-T) *blocked by GABAculine
← Succinate Semialdehyde
←  (SSDH) *blocked by Valproate
← Succinate
←
← Valproate strongly facilitates CNS inhibition
 It facilitates the GAD enzyme and prevents the breakdown of GABA. This
increases the transfer from Glu  GABA. This causes inhibition!
←
← GABA Transporters (GAT) Pharmacology
 VGAT (vesicular GABA transporter): GABA
o Nipecotate
o Vigabatrin
 GAT1 (neuronal, glial): GABA
o Nipecotate
 GAT2 (pia, arachnoid): GABA, Beta-alanine
o Nipecotate
 GAT3 (neuronal, glial): GABA, Beta-alanine
o Nipecotate
←
← GABAergic synapse
 Package GABA into vesicles and release it onto GABARs that generate IPSPs.
Presynaptically there was an action potential. GABABR are found posynaptically
and presynaptically. There are differences in their interaction tho. The GABA can
be transported back presynaptically and it can be transported into mitochondria
or broken down they can also be broken down in glial cells.
←
←
←
←
←
← Two Subunits: Co-expression
 GABA B receptors are obligate hetero-dimers: one GABA b1 and one
GABAb2 subunits are needed. One binds the g-protein and one binds to
the GABA.
 GABA b1 and GABA b2 subunits exist and co-expressed in the same cells and
regions and rate.
 If you only express GABA b1 then they are stuck in the endoplasmic membrane
and doesn’t make it to the plasma membrane. If only gabab2 are expressed
then the GABA doesn’t interact with the receptor.
←
← GABABR-Effector coupling
 GABA binds to one of the two components of the dimmer and activating the g-
protein on the other part of the dimmer.
 The Gi/o family of proteins;
o The α subunit ↓ the AC
o The βγ subunit ↓ VDCCs (blocking depolarization) and ↑ the activity of
VDKC (decreases the resting potential).
 PTX (pertussis toxin blocks the Gi/o Proteins).
←
← GABABR ligands
 AGO
o GABA (endogenous)
o Baclofen (exogenous antispasmatic drug)
 ANT
o Phaclofen
o 2-OHsaclofen
←
← Effects of divalent cations on GABABR ligands binding
 Some enhance GABA binding
o Mn2+ = NI2+ >Mg2+ >Ca2+
o Physiological [Mg2+] or [Ca2+
 Some inhibit GABA binding
o Hg2+ > Pb2+

Phosophorylation of GABABRs enhances βγ coupling to GIRKs; enhanced dissociation of βγ

from Rs. The phosphorylation of the dimmer causes the G protein to dissociate.
←
← GABABR block of VDCC via Go βγ subunits
 Antibody for βγ -Go will block the affect of Baclofen
←
← Presynaptic GABABR  postsynaptic GABA IPSPs
 GABA will inhibits it’s own release with autoreceptor effect. If you block the
presynaptic GABABR Gi  paired pulse suppression/depression.
←
← GABABR activates slow IPSC
 Slow outward K+ current: GIRK (more than ½ seconds) found postsynaptically in
neurons
 mAChRs
Found in:
LTN = laterodorsal tegmental n.
NDB = n. diagonal band
MS = medical septum
H = Habenula
NBM – N Basilis of Meynert
ACh is involved blood pressure regulation and

Biosynthesis: ChAT (choline acetyl transferase) positive cholinergic neurons

Degradation: Multiple isoforms of AChE (Aceylcholinesterase)

**it is NOT taken up by glial cells or reuptaken. It is degraded in the synapse.

ACh biosynthesis and metabolism

Acetyl CoA + Choline
 ChAT
ACh + CoA
 AChE
Acetate and Choline

AChE ligands I: Organophosphates – the ACh is left inside the synapse and the AChE
isn’t able to do its job.
Ligand Duration Use (dose dependant)
Long Irreversible Insecticide WMD
Sarin [GB] X X
DDT X X
Diazinon X X
Malathion X X

AChE Ligands II: Clinical AChE drugs

Inhibitor Duration
Short Long
Donepezil (Aricept) X
Physostigmine X

Regenerator of AChE Duration

activity Short Long
Obidoxime X

Vesicular ACh transporter (VAChT) – proton dependant (requires 2 protons per

molecule of ACh. Protons must be pumped in via an ATPase from the cytoplasm into the
vesicle along with ATP via an ATP transporter.

5 Classes of mAChRs
Name M1 M2 M3 M4 M5
Effectors Gq Gi Gq Gi Gq
Evens Odds
- ↓ AC - ↑ PLC
- Modulate IM
Uses/abuses of mAChR ligands
- Clinical
o reduce secretions (atropine)
o prevent motion sickness (scopolamine)
o treat Alzheimer’s (Donepezil)
o treat autonomic disorders (M3 ANT)
o dilate pupils for ophthalmic exams (M3 ANT)
o treat severe diarrhea (M3 ANT)
o slow heart rate (M2 AGO)
o treat mushroom/anti-AChE poisoning (atropine)

- Non-clinical
o dilate pupils for beauty (atropine)

*Newly discovered –allosteric modulation

- Brucine: enhance muscarinic agonist binding

mAChR Agonists
LIGAND Receptors
M1 M2 M3 M4 M5
Acetylcholine X X X X X
(ACh)
Carbachol X X X X X
Muscarine X X X X X
Oxotremorine X X X X X
Pilocarpin E X
mAChR Antagonists
LIGAND Receptors
M1 M2 M3 M4 M5
Atropine E X X X X X
Scopolamine X X X X X
Pirenzepine X
Gallamine X
4-DAMP X
Tropicamide X
Smooth muscle contraction via M3 mAChRs via IP3R mediated Ca2+ nM muscarine

Extremely slow IPSPs via M2 AChRs

Onset 30-90 s after mAChR ligand binding; amplitude 2-3 x normal AHP; GIRKs: Gi βϒ
subunits
A
fter-depolarization; Ca2+ spikes (M1,3 mAChRs)
Activating T-Type Ca2+ channels
Slow depolarization: Gq βϒ subunits
Block of sAHP by m1, 5 AChRs
Block of HVA VDCCs by M1, 3 Rs
Mediated by Gq α subunits
Im block by muscarinic agonists
Gq α subunits
Dopamine (DA)
Central DA minergic pathways
MFB – medial forbrain bundle (path from the SN and VTA to the rest of brain)
SN - Substantia Nigra  basal ganglia
VTA - Ventral Tegmental Area  the rest of the brain

Catecholamine biosynthesis
Tyr (tyrosine crosses BBB)
 TH (tyrosine hydroxylase)
DOPA
 AAAKC or DDC
Dopamine (in the VTA and SN this is the end)
 DA Beta hydroxylase
Norepinephrine (adonergic)
 PNMT
epinephrine (in adrenal cortex)
TH: The rate limiting enzyme
- it has several amino acids that can be phosphorylated. Cam-KII, PKA, PKC, ERK, and cdc-
like-K. PHosphorylating increases activity and phosphotases decrease activity.

Transmitters vs false transmitters

L-DOPA is converted into DA via AAADC. False neurotransmitter (alpha-methyl-DA) is
created by the same enzyme. DbetaH converts it into alpha methyl NE

DA degradation
DA
COMT MAO + aldehyde deOH
3-methoxy-tyramine DOPAC
MAO   COMT
HVA

Uses and abuses of DAminergic ligands

- appetite suppression
- antidepressants
- antipsychotics (including treatment of schizophrenia)
- fatigue suppression
- enhance attention
 - treating motor dysfunctions (parkinsons)
- pressor effects
Recreational
- fatigue suppression
- enhanced attention
- mania mimicry
- mild hallucinogenic effects

Biogenic amine hypotheses of affect/psychosis

As you age your biogenic amine are reduced… may lead to depression. All three seratonin,
dopamine, norepinephrine are involved in mood, emotion. And cognitive function

VTA  frontal ctx – hypo (negative symptoms)

VTA  Nucleus accumbens – hyper (positive symptoms)

Transporters; Vesicular DAT (VDAT)

 12 transmembrane segments and proton-dependent transport.
 Only requires one proton (ATPase)
 ATP site is outside the vesicle so no ATP import is required.

Vesicular Transport inhibitors (block filling of ALL biogenic amines)

- Reserpine – most widely used

Synaptic DAT (DA back into the cell)

 12 transmembrane protein.
 Na/CL-dependent transport;
 Oubain indirectly inhibits it, by blocking Na+/K+-ATPases.

Reuptake inhibitors
 DAT NET SERT
(DA transports) (NE transporter) (5-HT transporter
Indatraline*
cocaine
Bupropion (wellbutrin)*
Nomifensine (merital) Reboxetine* Fluoxetine* (frozac)
Duloxetine (cymbalta) Atomoxetine** Sertraline* (Zoloft)
Amphetamine Imipramine* Citalopram* (Celeza)
Amitriptyline* Paroxetine*** (Paxil)
Fluvoxamine*** (Luvox)
Venlafaxine*
Clomipramine***
  *antidepressants
 ** ADHD
 *** anxiolytics/antiOCD

Amphetamine and analogs

Amphetamine, detroamphetamine, methamphetamine
Analogs – methylphenidate (Ritalin), cocaine, phenmetrazine, MDMA

Amphetamines increase synaptic DA

Block reuptake in 2 ways
1. compete for DAT
2. upregulate MAP-K  phosphorylate DAT internalize DAT

DA-specific neurotoxins
 MPTP  glial MAO-B  MPP+ (shuts down kreb cycle in mitochondria)
 6-OH-DA
1. Both MPP and 6OH DA are substrates for DAT
2. Both are then taken into mitochondria
3. Both block oxidative metabolism
4. Both kill DA neurons selectively and dose-dependently
5. Both produce behavioral effects mimicking Parkinsonism

DARs are diverse!!

7 transmembrane segments; mono-, di-, and heterodi-meric (s. SST
(somatostatin), etc)

DAR types
Name D1 D2 D3 D4 D5
Synaptic Post- Pre- and Post- Post- Post-
location Post-
Alpha Gs Gi Gs
subunit
effector
Beta Decrease
gamma VDCC, VDKC,
subunits CDKC
effects
The ctx has D1-D5
Hypothalamus has D3 + D5
Corpus striatum has D1 + D2

DA agonists
Ligand Other catecholamine
DA receptor type
receptors
D1 D2 D3 D4 D5 Alpha beta
Dopamine X X X X X X
Apomorphine X X X X X
Dihydrexidine XX X
Bromocriptine X X X
Praminpexole X XX
Ropinirole X XX
DAR antagonists
Ligand DA receptor type
D1 D2 D3 D4 D5
Spiperone XXX XXX XX XX XX
Ecopipam X
Amisulpride XXX X
Chlorpromazine* XX X X
Trifluoperazine* XX X X
Haloperidol* XX X X
Resperidone* XX X X
*out-patient drugs

Tardive dyskinesia – intermittent inability to move. The receptors increases and then
they can’t create more. They are taken off neuroleptic drugs they return to the drugs after
symptoms of origional problem comes back.

Norepinephrine (NE)

Adreneric projections in the CNS

LC = Locus coeruleus - cerebellum
A1-A9 = reticular adrenergic nuclei – regulatory on the hypothalamus

Methods to alter transmission**

- Alter synthesis
o facilitate, block, false transmitters
 - Block vesicular storage
- Block release == Ca2+ blockers, etc.
- Direct receptor effects
o agonists, antagonists, suicide antagonists
- Block reuptake
- Block degradation

Uses/abuses of NE ligands
- Clinical
o Cardiac regulation (rhythm, rate, volume)
o Antihypertensive
o Bronchial dilation (asthma relief)
o Anti-depressant
o Anti-ADHD/ADD
o Anti-OCD
o Decongestant
- Recreational
o Hallucinogenic
o Amphetamine-like effects

Release blockers indirectly effect VNETs (vesicular norepinephrine transporters)

- block Mg2+-ATPase proton pumps specific to NE neurons
- do not cross BBB; anti-hypertensive (guan-), block arrhythmias (bretylim)
- Sympathetic
- It is proton dependant
Degradation inhibitors (-Is)
Enzyme MAO-I COMT-I
A-specific A- or B- B- specific
(NE, 5-HT) (nonspecific) (DA, HA)
Inhibitor Reversible Irreversible
Befloxatone Harmaline Iproniazid Deprenyl tocapone
MAO-Is are still prescribed as antidepressants

Deprenyl in phase III for Alzheimer’s

**MAO-A doesn’t have A’s in abr. (NE, 5HT)

**MAO-B has the A’s (DA, HA)

Classes of adrenoceptors (NE, EPI)

- alpha
o α1: smooth muscle contraction - Gq
o α2: smooth muscle contraction – Gi (inhibiting neurotransmitter release)
- beta: cardiac muscle contraction - Gs

Alpha 1 (α 1) Adrenoceptors
Name α 1D
α 1A α 1B
Expressed in: CNS, heart, liver, Resistance vessels, CNS, aorta, lung,
(don’t need to know) urogential smooth kidney, spleen bladder
muscle
Non-selective AGO DA
NE
EPI
Phenylephrine (nyquil)
Ephedrine, Pseudoephedrine
Selective AGO Tetrahydrozoline
(eyedrops)

Selective ANT Niguldipine Cycloazosin

(don’t need to know) 5-methylurapadil Spiperone
Non-selective ANT Phentolamine
Prazosin
Suicide ANT Phenoxybenzamine
G-protein Gq - ↑ IP3/DAG
Alpha 2 (α 2) Adrenoceptors
Name α2A α2B α2C
Expressed in: CNS, Lung, vascular Thalamus, liver, CNS, lung
muscle vascular, spleen
Function Autoreceptor; Vasoconstriction Undeterimined
Vasoconstriction,
sedation, analgesia,
anesthesia
Non-selective AGO NE
EPI
Clonidine
Selective partial LSD-25
AGO
Nonselective ANT Phentolamine
Prazosin
Yohimbine
α -subunit Gi
β-ϒ subunits Inhibit VDCCs, activate CDKCs
Antihypertensive vasodilators (alpha ANT)

Phenylethylamine hallucinogen relatives of NE

- LSD
- cathine
- ephedrine
- yohimbine
- mescaline
- elimicin

Beta (β) Adrenoceptors

Name β1 β2 β3
Expressed in: Neuronal cardiac, Neuronal, cardiac, Neuronal, cardiac,
kidney bronchial adipose
Non-Selective AGO NE
EPI
Isoproterenol
Ephedrine
Selective AGO Xamoterol Albuterol
Salmeterol
Selective ANT Atenolol Butozamine
Non-Selective ANT Propranolol
G-protein Gs - ↑ cAMP
Sympathetic effects on cardiovascular system
- Increases VDCC (HVA) and increases VDKC (IK) and increases VDCC (LVA) resulting
in each heart beat is going be faster and stronger. Bigger volume of blood pumped
harder each time. (acute effects)
- The higher blood pressure sustained causes issues also.

Antihypertensives (β1 ANT)

Atenolol – used to lower blood pressure.
**notice the suffix -olol

Brochodilators (β2 AGO)

Albuterol
Salmeterol
**notice the suffix –terol

Serotonin (5-HT)
Peripheral 5HT
- first purified from blood plasma (serotonin): 1948 and first purified from the brain in
1957
- total quantity of the body < 10 mg (5% of that in brain)
- Intestines 0 enterochromaffin cells enhance motility of 5HT4
- Blood vessels – platelets; vasoconstriction: 5HT1D
- Also a mitogen: enhances cell proliferation in muscle, liver but not in the bone

5HT pathways: Raphe n. which are widely distributed from the pons down the brainstem
and project throughout the rest of the brain. The largest are the dorsal and median Raphe
n. They are pyramidal neurons and they have afterhyperpolarization (modulated by
apamine). These neurons are important in the sleep/wake cycle. They are almost
completely silent when sleeping and active during waking.

Hertogeneous 5HT fiber systems

 - Doral Raphe n. has diffuse projections
- Median Raphe n. has specific projections

Serotonin (5HT) synthesis and metabolism

Compound Enzyme Inhibitors
L-tryptophan
Tryptophan hydroxylase Fenfluramine
↓
(TrpH)
L-tryptamine (Tra)
α aromatic amino acid Carbidopa
↓ decarboxylase (DDC or
AAADC)
5hydroxytryptamine (5HT)
Monoamine oxidase MAO-A inhibitors
↓
(MAO-A)
5-hydroxyindoleacetaldehyde
Aldehyde dehydrogenase
↓
(AD)
5-hydroxyindoleacetate (5-HIAA)
SERTs
- ATPase pumps protons into the vesicle
- SERTs pump 5HT and Na+ & Cl- into the vesicle and 5HT and K+ outside the vesicle

5HT1Rs
5-HT1A 5-HT1B 5-HT1D 5-HT1e 5-
HT1f
Tissue Neuronal; smooth Rodent neuronal Human Widely distributed
muscle autoreceptor; neuronal
smooth muscle autoreceptor;
constriction smooth
muscle
constriction
Ubiquitous 5-HT
agonist Quipazine
Selective Buspirone Ergotamine (mold)
full agonists DMT Sumatriptan
(dimetheyltryptamine)
Selective Spiperone Isamoltane
antagonists
Antagonist Pindolol
G-Protein G i/o
Anziolytic (5HT1a agonist) – Buspirone

Migraine therapy (5HT1b/1d agonists)

- Ergotamine – hallucinogen
- sumatriptan
**cause vasoconstriction – stabilization of either state… can feel dull; but reduces migraines

5-HT2Rs
5-HT2A 5-HT2B 5-HT2C
Nonselective 5HT
AGO Quipazine
Partial AGO LSD-25 LSD-25
Psilocybin/psilocin Psilocybin/psilocin
Pyschedelic Pyschedelic
phenylethylamines phenylethylamines
Selective DMT agomelatine
AGO DOM (STP)
Selective ANT Ketanserin Metergoline ritanserin
Nonselective Mesulergine
ANT dibenzyline
G-Protein Gq

Psychedelic effects mediated by 5HT2ARs

- competitive antagonists do not block psychedelic effects

Indolaminergic psychedelics (5HT2A AGO)

 - DMT
- Psilocybin
- LSD-25

Clinical use of 5-HT2 ligands

- satiety stimulants (5HT2C AGO)
- anti-schizophrenic (5HT2A ANT)

5HT3Rs
5HT3Rs
Nonselective AGO 5HT
Quipazine
Selective AGO CBG
Selective ANT Ondansetron (keeps you from vomiting)
Zacopride
Mechansism Petameric cation channel (weak selectivity
for Na+)
Antiemetics (5HT3 antagonists) – used extensively to alleviate nausea in chemotherapy

- Ondansetron
- Zacopride
- also used in IBS treatment

Nootropics (5HT3 antagonists) – the problems is they don’t cross the BBB and would cost
$100/dose/day to take enough drugs to cause the nootropic effects.

5HT4-like receptors
5HT4 5HT6 5HT7
Nonselective 5HT
agonists Quipazine
Selective AGO EMDT COAT
Selective ANT Amoxipine
Nonselective ANT Clozapine
G-protein Gs

5HT5Rs
5-ht5a 5ht5b
Nonselective AGO 5HT
LSD
5HT specific neurotoxin
- PCPA: highly specific for 5HT neurons similar in mechanism to MPP+
Melatonin - just know that it is serotonin synthesizes melatonin in pineal
←
← Histamine
← Peripheral HA
← - Inflamation (in mast cells): H1Rs
 orgasm
 allergy
 congestion
← - Digestion: H2Rs
 gastrin
 Parietal cells create gastric acid
← - Immune Response: H4Rs
 basophils
 neutrophils
 bone marrow
←
← HAminergic neurons: transport, synthesis, degradation
 L-amino acid transporter takes HA into the cell (AAAT)
 Histidine is converted by histidine decarboxylase (HD) into histamine and
transported into vesicles via Vesicular MonoAmine Transporter (VMAT).
 Histamine methyltransferase (HAMT) breaks down histamine into
telemethylhistamine
←
← CNS HA: Hypothalamic tuberomamillary nuclei* (TMN) project to the
rest of the body.
← *(right above the mamilary bodies)
←
← Tuberomamillary neurons (TMN)
← - large soma, dendrites
- long thin poorly myelinated punctate axons (slow, large number of synapes
← - adjacent to VLH hypocretin (hypothalamus cretine neurons)

HA: Role in waking and sleep.

 The firing rate is high when you are awake and drops during SWS and almost turns
off during REM.

Antihistamines make you lethargic

Modafinil – increases HA release, increases alertness

HAR Types
Receptor H1 H2 H3 H4
g-protein Gq Gs Gi Gi
Neuronal Postsynaptic Postsynaptic Presynaptic postsynaptic -
location
Global Waking state; Waking state; Autoreceptor; ? -
Function arousal; appetite arousal regulate
suppression learning and transmission;
memory inhibit -waking
arousal
Other Mast cells Parietal cells Basophils;
Tissues neurophils;
bone
marrow;
smooth
muscle
Peripheral Inflammation; Acid release allergies
Function congestion;
orgasm
H3 is the only autoreceptor.
- If you block the receptor you increase firing rate of the postsynaptic neuron.
- H3 presynaptic block of Voltage Dependent Ca Channels.
- An AGO will decrease the inward current through VDCCs.
- Autoreceptors act like this
-

Uses/potentials of HA ligands
- Peripheral
o Allergy treatments (peripheral H1 ANT)
o Anti-congestive (peripheral H1 ANT)
o Anti-inflammatory (peripheral H1 ANT)
o Antacids (peripheral H2 ANT) *not really antiacids but go the problem of the
acid.
- Central
o Anti-emetics/anti-vertigo (H1 ANT)
o Hibernation, sleep (H1 ANT)
o Stimulants (H3 ANT)
o Alzheimer’s therapies (H3 ANT)
o Nootropics (H3 ANT)
o ADD therapies (H3 ANT)
o Anti-obesity treatments (H3 ANT)

HA Agonists
Competitive Agonist HAR
H1 H2 H3 H4
Histamine (HA) X X X X
Dimaprit X
Proxyfan (partial) X
Imetit X X
Classic antihistamines: Competitive ANT
Competitive ANT HAR
H1 H2 H3 H4
Cetirizine* (zyrtec) X
Clorpheniramine* X
Dimenhydrinate** (Dramamine) X
Diphenhydramine* (Benadryl) X
Doxylamine*** (Unisom) X
Fexofenadine* (Allegra) X
Loratadine* (Claritin) X
Meclizine** (Antivert) X
Promethazine** (phenergan) X
*allergy meds
**anti vestibular
***Sleeping pills

Other HAR antagonists, inverse agonists

Competitive ANT HAR
H1 H2 H3 H4
Cimetidine (tagamet) X
Clobenpropit X
Inverse AGO ***Increases Neurotransmitter Release… similar to the
antagonist.
Thioperamide X
H2 agonists increase CA1 excitability
- If the H2 agonists is administered there is no afterhyperpolarization

H3 antagonists: nootropic and dietary benefits…. Every learning task the H3 has
shown to enhance.

Exam… know the receptors, antagonist, non-competitive. Know the

mechanism of action. Know the clinical uses… digestion, asthma, and heart
rate information. Know the biosynthesis and the degradation of the
neurotransmitters and their enzyme and rate limiting…. Know the
transports- vesicular and cell membrane transporters. Know the drugs that
blocks NETS SERTS ECT.