Department of Pharmacology AUTOCOIDS BY Mohammed Q. Mal-Allah Department of Pharmacology College of Medicine

Definition: Auto = self Coids = Remedy or some times called Local Hormones Why are they very important?

Classifications: A. Amine Autociods: 1. Histamine 2. Serotonin B. Eicosanoids (PGs; Thromboxane ; Leukotriens) C. Peptides Autociods: 1)Kinins 2) Renin; Angiotensins etc) 4. Endogenous peptides (Kinins; Renin; Angiotensins etc)

Serotonin Is serotonin as important as N.E or Histamine? Definition and Location: it is a neurotransmitter found in enterochromaffin cells in GIT (90%) , and in plateletes and in raphe nuclei of brain stem. Is serotonin as important as N.E or Histamine?

Mechanism of action : Interacts with 12 receptor subtypes Why is 5-HT3 receptor differs from other 5- HT receptors?

Pharmacological actions of Serotonin CVS: 1) Blood vessels: Potent and direct contractions on smooth muscle (via 5- HT2 ) EXCEPT : Skeletal Muscles and Heart blood vessels. Note : 5- HT can give rise to triple action: Decrease BP due to chemoreceptor response then increase BP due to Vasoconstriction (5-HT2), then decrease B.P due to skeletal muscle V.D 2) Platelet: Increase platelet aggregation via 5-HT2

GIT: 1) increase contraction of smooth muscle (via 5- HT4 stimulated the release of ACH). What is the clinical significant? 2) Nausea and vomiting (via 5-HT3) therefore 5-HT3 antagonists are used for RX of ? Respiration : 5-HT may produce weak bronchoconstriction. CNS: very important.(Appetite; depression and mania; Pain; Anxiety; Schizophrenia).

Clinical Uses of Serotonergic Drugs: Note1: Unlike NE or DA, serotonin its self has no clinical uses, however, its agonists and antagonists have very important therapeutic applications. Note 2: Unlike histamine where only its antagonists are used, serotonin agonists and antagonists can be used.

Clin. Uses of Serotonergic Agonists: 1) Buspirone: 5-HT1A agonist used as anxiolytic agent. 2) Sumatriptan: 5-HT1D agonist for migraine (Treatment and prophylactic). 3) Metoclopromide (Plasil): 5-HT4 agonist as prokinetic agent (for Rx of gastroesophagial reflex). And also used for N/V via 5-HT3 antagonistic action. 4) Dexfenfuramine: Acts by stim. Release and inhib. Reuptake of serotonin. Used as anorexic agent. What is the effect of serotonin antagonists on appetite?

Clinical Uses of Serotonergic Antagonists: 1) Ondansetron & Granisetron: 5-HT3 antagonists Common used for Rx of N/V induced by cytotoxic (chemotherapy) drugs. 2) Cyproheptadine: Both H1, 5-HT1,2 and cholinergic antagonist used for Rx carcinoid tumor (significant increases in serotonin) and to increase appetite.. 3) Ketanserin: 5-HT2/1c antagonist and a1-adrenergic blocker. (used as antihypertensive agent) 4) Methysergide: This is an ergot alkaloid acts as 5-HT1,2 antagonist used for Rx of migraine.

C. Vasoactive Peptides A. Vasoconstrictors (angiotensin II; vasopressin; endothelins and neuropeptide Y. B. Vasodilators (Bradykinin and related Kinins; Natriuretic Pepties; Vasoactive Intestinal Peptide; substance P; Neurotensin)

Vasodialtion may be due to: I. A direct inhibitory effect of kinins on the arteriolar smooth m. II. May be mediated by the release of vasodilator PGS(E2 & I2).

b. The predominant effect of kinins on veins is contraction & may be due to: 1-direct stimulation of venous smooth m .. or 2- due to the release of vasoconstrictor PGs(F2 α).

Ergotamine (Metograine®)

Bromocriptine (Parlodel®)

Cabergoline (Dostinex®)

Lysuride (Dopergin®)

Ergometrine (Ergonovine) (Methergin®)

Sumatriptan (Imigran®)

Captopril (Capoten®)

Losartan (CozAAr®)

Buspirone (Buspar®)

Tegaserod (Zelmac®)

Cyproheptadine (Phenergan®)

Pizotyline or Pizotifen (Mosegor®)

Ondansetron (Zofran®)

Granisetron (Kytril®)