1. Dopaminergic agents Medicinal Chemistry 2018-2019 4th Year
Drugs Acting On CNS
Dopaminergic agents
Medicinal Chemistry
th Year
Mohammed N. Sabir
College of Pharmacy-UOS

2. Your reference…
Chapters 12 & 13

3. Introduction…
The majority of CNS drugs act on specific receptors that modulate synaptic transmission, however; anesthetics and alcohol exhibit non-specific action.

4. Introduction… Their are two types of channels:-
Their are two types of channels:-
Voltage-gated ion channels
Ligand gated (ionotropic receptors)

5. Introduction…
Dopamine (DA) is a CNS NT controlling emotion, movement and reward mechanisms and is metabolic precursor for EN and NE.

6. Introduction…
DA production from L-Tyrosine

7. Introduction…
DA storage & release… D2
DAT D1

8. Introduction…
Modulation of DA release and DA receptors…

9. Introduction…
D1 receptors family D2 receptors family

10. D1 & D2-receptors DA superimposition on D1/D2 receptors domain…

11. Introduction…
Postsynaptic DA receptors and subtypes, (GABA)ergic, Glutaminergic and Cholinergic.

12. Introduction…
DA transporter (deactivator)

13. Dopaminergic pathways in brain…
Nigrostriatal
Mesocortical
Mesolimbic
Tuberohypophyseal

14. Introduction…
Parkinson Disease (PD) and DA neurons.

15. Introduction…
DA metabolism - MAO - COMT

16. Introduction…
HVA & DOPAC

17. Introduction… DA pathways in brain Nigrastriatal Mesocortical
Mesolimbic
Tuberohypophyseal

18. Parkinson disease (PD)

19. Antiparkinson agents…
PD & L-Dopa/Carbidopa

20. SAR & metabolism of L-Dopa and Carbidopa

21. Selective MAO-Is…
MAO-Is - Selegiline - Rasagiline

22. MAO-I
SAR & Metabolism

23. DA agonists…
Ergot derivatives
Pergolide
Cabergolide
Bromocriptine

24. DA agonists…
SAR & Metabolism

25. DA agonists… Nonergot derivatives Apomorphine Pramipexole Rapinirole
Rotigotine

26. DA agonists…
SAR & Metabolism

27. DA agonists…
COMT-Inhibitors Tolcapon Entacapone

28. DA agonists…
SAR & Metabolism

29. Antipsychotic agents…
Disease state and causes
DA hypothesis of Schizophrenia (DHS)
D1, D2 receptors, DA, Glutamate and serotonin

30. Antipsychotic agents…
1st generation antipsychotics…
1-Phenothiazenes
2-Thioxanthenes
3-Butyrophenones
4-Dihydroindolones (Molindone)

31. 1st generation antipsychotics…
Phenothiazenes

32. 1st generation antipsychotics…
Phenothiazenes

33. 1st generation antipsychotics…
Phenothiazenes SAR…

34. 1st generation antipsychotics…
Thioxanthenes

35. 1st generation antipsychotics…
Thioxanthenes
Thioxanthene
Chlorprothixene

36. 1st generation antipsychotics…
Thioxanthenes
SAR & Metabolism

37. 1st generation antipsychotics…
Phase I reaction
Oxidative N-demethyhlation
Aromatic hydroxylation
Tertiary amine oxidation of the side chain
Oxidative deamination
N-10 Alkylation

38. 1st generation antipsychotics…
Butyrophenones and related agents - Haloperidol - Droperidol - Pimozide

39. 1st generation antipsychotics…
Haloperidol

40. 1st generation antipsychotics…
Droperidol

41. 1st generation antipsychotics…
Pimozide

42. 1st generation antipsychotics…
Metabolism of butyrophenones
1st pass mechanism include:-
N-dealkylation
Reduction (ketone)
Oxidation
N-Oxidation

43. 1st generation antipsychotics…
Haloperidol decanoate