Dopaminergic agents Medicinal Chemistry 2018-2019 4th Year Drugs Acting On CNS Dopaminergic agents Medicinal Chemistry 2018-2019 4th Year Mohammed N. Sabir College of Pharmacy-UOS mohammed.sabir@univsul.edu.iq
Your reference… Chapters 12 & 13
Introduction… The majority of CNS drugs act on specific receptors that modulate synaptic transmission, however; anesthetics and alcohol exhibit non-specific action.
Introduction… Their are two types of channels:- www.zoology.ubc.ca. Their are two types of channels:- Voltage-gated ion channels Ligand gated (ionotropic receptors) www.dreamstime.com
Introduction… Dopamine (DA) is a CNS NT controlling emotion, movement and reward mechanisms and is metabolic precursor for EN and NE.
Introduction… DA production from L-Tyrosine
Introduction… DA storage & release… D2 DAT D1
Introduction… Modulation of DA release and DA receptors…
Introduction… D1 receptors family D2 receptors family
D1 & D2-receptors DA superimposition on D1/D2 receptors domain… https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiTlrqrz-
Introduction… Postsynaptic DA receptors and subtypes, (GABA)ergic, Glutaminergic and Cholinergic.
Introduction… DA transporter (deactivator)
Dopaminergic pathways in brain… Nigrostriatal Mesocortical Mesolimbic Tuberohypophyseal
Introduction… Parkinson Disease (PD) and DA neurons.
Introduction… DA metabolism - MAO - COMT
Introduction… HVA & DOPAC
Introduction… DA pathways in brain Nigrastriatal Mesocortical Mesolimbic Tuberohypophyseal
Parkinson disease (PD)
Antiparkinson agents… PD & L-Dopa/Carbidopa
SAR & metabolism of L-Dopa and Carbidopa
Selective MAO-Is… MAO-Is - Selegiline - Rasagiline
MAO-I SAR & Metabolism
DA agonists… Ergot derivatives Pergolide Cabergolide Bromocriptine
DA agonists… SAR & Metabolism
DA agonists… Nonergot derivatives Apomorphine Pramipexole Rapinirole Rotigotine
DA agonists… SAR & Metabolism
DA agonists… COMT-Inhibitors Tolcapon Entacapone
DA agonists… SAR & Metabolism
Antipsychotic agents… Disease state and causes DA hypothesis of Schizophrenia (DHS) D1, D2 receptors, DA, Glutamate and serotonin
Antipsychotic agents… 1st generation antipsychotics… 1-Phenothiazenes 2-Thioxanthenes 3-Butyrophenones 4-Dihydroindolones (Molindone)
1st generation antipsychotics… Phenothiazenes
1st generation antipsychotics… Phenothiazenes
1st generation antipsychotics… Phenothiazenes SAR…
1st generation antipsychotics… Thioxanthenes
1st generation antipsychotics… Thioxanthenes Thioxanthene Chlorprothixene
1st generation antipsychotics… Thioxanthenes SAR & Metabolism
1st generation antipsychotics… Phase I reaction Oxidative N-demethyhlation Aromatic hydroxylation Tertiary amine oxidation of the side chain Oxidative deamination N-10 Alkylation
1st generation antipsychotics… Butyrophenones and related agents - Haloperidol - Droperidol - Pimozide
1st generation antipsychotics… Haloperidol
1st generation antipsychotics… Droperidol
1st generation antipsychotics… Pimozide
1st generation antipsychotics… Metabolism of butyrophenones 1st pass mechanism include:- N-dealkylation Reduction (ketone) Oxidation N-Oxidation
1st generation antipsychotics… Haloperidol decanoate