Glu transporters Vesicular ACh GAT1/2/3 VGAT (vesicular Vesicular DAT V NET V SET Synaptic DAT Synaptic NET Synaptic 5HT V HA Synaptic
Transporter GAT) HA
(VAChT)

Structure 1 Na Dependent: ATP transporter 1/3 = neuronal,   ATPase outside ATPase outside ATPase 2xNa, 1xCl VMAT AAAT
EAAC-1 ATPase from glial 1H/1DA Mg req outside, are needed to
GLT-1 inside 2 = pia, Mg not req 1H/1NE Mg not req get 1xDA back
GLAST 2H per ACh arachnoid into the cell.
2 Na and H Dep pumped in.   Na gradient is
Gln-T generated by
3 Mg and H Dep Na/K ATPase
VGluT (ATPase?) (blocked by
ouabain)

Inhibitor N/A N/A Nipecotate Nipecotate Reserpine = no Guanethedine Cocaine, Indatraline

Vigabatrin DA/NE/5HT/HI Guanadrel (anti-
packaging hypertensive) Bupropion (Wellbutrin)
Bretylium (block
arrhythmias) Venlafaxine, Clomipramine
They all block Mg
dependent Nomifensine Reboxetine Fluoxetine
ATPase. Duloxetine Atomoxetine Sertraline
Amphetamine Imipramine Citalopram
Amitriptyline Paroxetine
Fluvoxamine

 Vesicular and Cell Membrane Transporters.

Amphetamines: Regional Gl G ACh DA NE 5HT HA

Amphetamines Production u A
Dextroamphetamine of NTs B
Methamphetamine A
Amphetamine analogs: Where 1. Laterodorsal tegmental Peripheral: Sympa 1.Locus Peripheral: Peripheral:
Methylphenidate (Ritalin) = ↑DA at jxns, which will stimulate underactivated regions in the nucleus following blood coeruleus 1. Intestines: 1. HAR1 → mast
brain, which will quiet down hyperactive regions 2. NDB(diagonal band vessels 2. Reticular enterochroma cells.
3. H= habenula Autocrine: kidneys, adrenergic nuclei ffin cells: 2. HAR2 →
Cocaine
intestines. (A1-A9) enhance Parietal cells
Phenmetrazine 4. N.basilis of
Central: motility 3.HAR4→
MDMA Meynert VTA = major source 2. platelets: Basophils,
Mechanism of action SNc vasoconstricti PMNs
↑ synaptic DA by blocking reuptake via: Arcuate n. on. CNS:
1.Competition for DAT CNS:
1. Raphe n.(pons
1. Hyp
2.Upregulation of MAP-K: leads to prylation and internalization of DAT othalamic
and BS):
DA neurotoxins: tubermammil
Dorsal =
MPTP: converted to MPP+ via MAO-B diffuse ary project to
Transported across BBB projections rest of CNS =
Taken up via DAT in SNc and shuts down Krebs cycle = cells die. and Median= HAR 1-4.
6-HydroxyDA same effect, used experimentally. specific
projections.
Receptor Structure:
mGluRs GABAbRs mAChRs DARs NE/EPI Rs 5HT Rs
Structure 7-transmembrane + 7 transmembrane + 1 7 trans. Segments:
1 extracellular extracellular binding Mono-, di, hetero-
binding domain. domain meric prots.
Homodimers = takes 2 subs coexpression:
2 Rs and 1xGlu to obligate heterodimer:
activate cascade. GABAR1 (a,b,c,d) binds
ligands
GABAR2 binds G-prot
Divalent cations are
required for ligand
binding:
Mn is potent for all exogen
Ca is only for GABA
Regional Expression GluR1 = Purkinje +
Hippocampus
GluR6 =
Hippocampus &
cortical region

 NE, EPI A1 A2 B  

Non-selective AGO NE, EPI NE,EPI NE,EPI  

Phenylephrine Clonidine Isoproterenol
Ephedrine Ephedrine
Pseudoephedrine

Non-selective ANT Phentolamine Phentolamine Propanolol  

Prazosin Prazosin
Yohimbine

Selective AGO A1a A2a (AutoRs) B1 B2 (bronchodilators)

  Tetrahydrazoline LSD-95 Xomoterol Albuterol

Salmeterol

Selective ANT B1(antihypertensive) B2

  Atenolol) Butoxamine

Suicide ANT All A1      

  Phenoxybenzamine      
 Serotoni 5HT1 5HT2 5HT3 5HT4-like 5HT5
n Rs

G-prot Gi/o Gq Pentameric Gs Unknow

cation
coupled n
Non- 5HT Same Same Same 5HT
selective Quipazine LSD-25
AGO

Selective 5HT1a 5HT1b 5HT1d  5HT2a 5HT2c CBG  5HT6 5HT7  

AGO
Buspirone Ergotamine Also DMT Agomelatine EMDT COAT
DMT (endo, Sumatriptan DOM/(STP)
hippocampus, Zolmitriptan
cingulate
cortex,
entorhinal
cortex
hallucinogenic

 Non-  Pindolol Mesulergine  N/A  5HT6 5HT7  

selective Dibenzyline
ANT Clozapine Same

 Selective  5HT1a 5HT1b 5HT1d  5HT2a 5HT2b 5HT2c  5HT3  5HT6  

ANT
Spiperone Isomoltane Same Ketanserin(a Metergoline Ritanserin Ondasetron Amoxipine
(increase NT nti- Zacopride (IBS)
release) hallucinating)

 Partial   5HT2a        
AGO
LSD-25
Psilocybin/Psilocin
Psychedelic
phenylethylamines
 Tissue 5HT1b 5HT1d        
 Rodent neuronal Human neuronal
Auto Rs
Auto Rs (↓NT release)
Sm.muscle constr.
Sm.muscle constr

Metabotropic fxns:
mGluRs GABAbRs mAChR DARs NERs SERs HARs
Metabotropic Class I: mGluR1/5: Gi/o: M1/3/5: Gq D1/5: Gs A1:Gq → sm.muscle HT1: Gi H1:Gq
effector fxn
Gq/o = PLC + by-Iahp block Gi a-sub→AC down M2/4: Gi D2/3/4: Gi and by-sub contraction HT2: Gq Postsynaptic: Waking state,
Class I activates neighboring NMDA Rs =cAMP↓ M3: Sm.muscle contraction: ↓VDCC, VDKC, CDKC HT3: cation Arousal, Appetite↓
via PKC/CAM KII + block Iahp By-sub→ block PostS L IP3 Ca release A2: Gi → sm.muscle HT4-like: Gs H2: Gs
 =↑excitability VDCC = ↓Ca-dep AP Activation T VDCC contraction + A2a Postsynaptic: Waking state,
Activate PLA2 → headache via By-sub→ block PreS P/Q M2: Cardiac muscle AutoRs = inhibition of learning and memory.
ara.acid. VDCC = ↓NT release = GIRK activation by Gi by-sub: NT release via by-sub H3:Gi
Presynaptic Rs block N type Ca via by- IPSC↓ (if AutoRs) slow IPSPs blockage of VDCC. Presynaptic:→
sub→ NT↓. By-sub → activate M1/3: B: Gs→ cardiac muscle AutoRs→ decrease NT
mGluR1 induce LTD of parallel GIRK/↑IPSC. Strong and AfterDPLZ: Ca spikes contraction release via by-sub inhibition
fiber/Purkinje cell synapse. long (1/2sec) duration of Activation T VDCC via Gq of VDCC
K current positive to by-sub Postsynaptic
Class II: mGluR2/3 -80mV. Prylation of Block HVA VDCC via Gq H4: Gi
Gi/o = cAMP down GABAbRs ↑ by-sub a-sub Postsynaptic.
GIRK activated dissociation and GIRK M1/3/5:
Ca channels blocked activation. Im is letting K out at rest
Can enhance Glu release via auto-Rs. Block via Gq a-sub activation
of PKC→ prylation shut and
Class III: mGluR4,6-8 Calcineurin = open again
Gi/o =cAMP down M1/5:
GIRK activated Block ISAHP via Gq a-sub
Ca channels blocked Thus, anti-AChE elements
(metrifonate) will↑ ACh
concentration and block
normal Isahp via mAChRs.
AGO: Class I GABA ALL: ACh, Carbachol, ALL: DA/Apomorphine ALL: Histamine
Glu/Ibotenate/DHPG Baclofen Muscarine, Oxotremorine, D1/5: Dihydrexidine H2: Dimaprit(↑digestion)
Class II M5:Pilocarpine D2/3/4: H3: Proxyfan(partial,
Glu/NAAG Bromocriptine ↑AutoRs)
Class III D2/3: H3/4: Imetit
Glu/AP4 Pramipexole/Ropinirole
ANT Class I Phaclofen ALL: Atropine, Scopolamine ALL: Spiperone H1: Dimenhydrinate /Meclizine/
CPG Saclofen/2-OH Saclofen M1: Pirenzepine D1: Ecopipam Promethazine→ motion sick,
Class II Ptx – “noncompetitive M2: Gallamine (attenuation of Doxylamine →sleep pill
Fexofenadine
EthGlu ANT”, inactivates ADP-Gi M3: 4-DAMP cocaine affects) Cetirizine,
Class III M4: Tropicamide D2/3: Amisulpride Chlorpheniramine
MAP4 D2/3/4: Loratadine
Trifluoperazine, Diphedramine
Haloperidol Inverse Agonist:
Risperidone H2: Cimetidine
H3: Clobenpropit, thioperamide
AGO: Generalized anxiety disorder + AGO: muscle relaxant AGO: Pilocarpine: Glaucoma= AGO: anti-Parkinson’s AGO: AGO:1a=anxiolyti AGO: ↑CA1 excitability by
Schizophrenia sphincter pupil contraction= and anti-RLS A2=Hallucinogenic/Psyc c; blocking Iahp
more humour outflow. ANT: hostimulants 2a= psychedelic ANT: Nootropic and dietary
ANT: M2: slow heart rate Antipsychotics/Neurol ANT: Antihypertensive 2c=satiety benefits.
M3 pupil dilation (atropine) eptic, esp. D2 ANT. NET blockers: stimulants
AChE blockers: Alzheimers DAT blockers: Antidepressants/ADHD/ ANT:
Psychostimulants/ADH Anxiolytic 5HT2a=antischiz
D treatment ophrenic.
(Methylphenidate) 5HT3=antiemetic
SERT blockers:
Antidepressants/
anti-OCD

1. 2-hydroxySaclofen 47. Phaclofen 90. EMDT

2. 4-DAMP 48. Phenmetrazine 91. Ephedrine
3. Ach 49. Phenmetrazine 92. Ephedrine
4. Agomelatine 50. Phenoxybenzamine 93. Ergotamine
5. Albuterol 51. Phentolamine 94. EthylGlu
6. Amisulpride 52. Phentolamine 95. Fluoxetine
7. Amitriptyline 53. Phenylephrine 96. Fluvoxamine
8. Amoxipine 54. Physostigmine 97. GABA
9. Amphetamine 55. Pilocarpine 98. GABAculine
10. Amphetamine 56. Pindolol 99. Gallamine
11. Amphetamine 57. Pirenzepine 100.Glu
12. AP4 58. Pramipexole 101.Glu
13. Apomorphine 59. Prazosin 102.Guanadrel
14. Atenolol 60. Prazosin 103.Guanethedine
15. Atomoxetine 61. Pseudoephedrine 104.Haloperidol
16. Atropine 62. Psilocin 105.HydroxyDA
17. Baclofen 63. Psilocybin 106.Ibotenate
18. Bretylium 64. Ptx 107.Imipramine
19. Bromocriptine 65. Quipazine 108.Indatraline
20. Brucine 66. Reboxetine 109.Indatraline
21. Bupropion 67. Reserpine 110.Isomoltane
22. Buproprion 68. Reserpine 111.Isoproterenol
23. Buspirone 69. Risperidone 112.Ketanserin
24. Butoxamine 70. Ritanserin 113.LSD-25
25. Carbachol 71. Ropinirole 114.LSD-25
26. Citalopram 72. Saclofen 115.LSD-95
27. Clomipramine 73. Salmeterol 116.Malathion
28. Clonidine 74. Sarin 117.MAP4
29. Clozapine 75. Scopolamine 118.MDMA
30. COAT 76. Sertraline 119.MDMA
31. Cocaine 77. Spiperone 120.Mesulergine
32. Cocaine 78. Spiperone 121.Metergoline
33. CPG 79. Sumatriptan 122.Methamphetamine
34. DDT 80. Tetrahydrazoline 123.Methylphenidate
35. Dextroamphetamine 81. Trifluoperazine 124.MPTP
36. DHPG 82. Tropicamide 125.Muscarine
37. Diazinon 83. Valproate (2-propylpentanoic acid) 126.NAAG
38. Dibenzyline 84. Venlafaxine 127.Nipecotate
39. Dihydrexidine 85. Vigabatrin 128.Nipecotate
40. DMT 86. Vigabatrin (4amino-5-hexenoic acid) 129.Nomifensine
41. DMT 87. Xomoterol 130.Nomifensine
42. DOM 88. Yohimbine 131.Obidoxime
43. Donepezil 89. Zacopride 132.Ondasetron
44. Duloxetine 133.Ouabain
45. Duloxetine 134.Oxotremorine
46. Ecopipam (attenuation of cocaine affects) 135.Paroxetine