Sumatriptan reduces the pain of migraine by acting as selective agonist of______ receptors?
Ans. c (5HT 1B/1D) (Ref. KDT, Pharmacology, 6th ed., 175)Sumatriptan is 5-HT1B/1D agonist. It inhibits trigeminal nerve activation; prevents vasoactive peptide release; induces vasoconstriction. Half-life < 2 hours. Uses: Acute migraine, cluster headache attacks. Adverse effects - Coronary spasm (contraindicated in patients with CAD or Prinzmetal angina), mild tingling.Important 5-HT Receptor SubtypesComments5-HT1Autoreceptors; inhibit serotonergic neural activity in brain.5-HT1A- present in raphe nuclei and hippocampus, BUSPIRONE may act through these receptors. 5-HT1B/1D - Constricts cranial blood vessels and inhibits release of inflammatory neuropeptides in them; SUMATRIPTAN acts through these receptors.5-HT2APreviously D type receptor; most important postjunctional receptor mediating direct actions of 5-HT like vascular and visceral smooth muscle contraction, platelet aggregation, neuronal activation in brain; KETANSERIN blocks these receptors.5-HT3Previously M type receptor; depolarizes neurones by gating cation channels; elicits reflex effects of 5-HT - emesis, gut peristalsis, bradycardia, transient hypotension, apnea, pain, itch; ONDANSETRON acts by blocking these receptors.5-HT4Mediate intestinal secretion, augmentation of peristalsis.RENZAPRIDE is a selective 5-HT4 agonist.Tegaserod is a new 5-HT4 partial agonist approved for the treatment of irritable bowel disease.Serotonin Receptor Subtypes.Receptor subtypeDistributionPostreceptor mechanismPartially selective agonistsPartially selective antagonists5-HT1aRaphe nuclei, hippocampusMultiple, Gi coupling dominates8-OH-DPATWAY 1006355-HT1BSubstantia nigra, globus pallidus basal gangliaGi., | cAMPCP93129 5-HT1Da,bBrainGi, | cAMPSumatriptan 5-HTIECortex, putamenGi, |cAMP 5-HTIFCOrtex, hippocampusGi, | cAMP 5-HTIPEnteric nervous systemGo, slow EPSP5-HydroxyindalpineRenzapride5-HT2APlatelets, smooth muscle, cerebral cortex, skeletalGq, IPa-Methyl-5-HTKetanerin5-HT2BStomach fundusGq, IP3a-Methyl-5-HTSB2047415-HT2CChoroid, hippocampus, substantia nigraGq IP3a-Methyl-l-HTMesulergina5-HT3Area postrema, sensory and entric nervesReceptor is a Na+-K+ ion channel2-Methyl-5-HT, m- chloropheny IbiguanideTropisetron, ondansetron, granisetron5-HT4CNS and myenteric neurons, smooth muscleG8,| cAMP5-Methoxytryptamine, renzapride, metoclopramide. 5-HT5A.BBrain| cAMP 5-HT6.7BrainG8,| cAMP Clozapine (S-HT,)Educational points:SEROTONIN (5-HT)# Made from Tryptophan# Can be metabolized to Melatonin# Raphe nucleus: to Forebrain, Striatum, Cortex, Hippocampus, Spinal Cord.# Actions:- 5-HT is a potent depolarizer of nerve endings.- It thus exerts direct as well as reflex and indirect effects.- Tachyphylaxis is common with repeated doses of 5-HT.# Diseases associated:# High 5-HIAA (& low 5-HT) related to suicide.# Affective behavior (.Depression);# | Appetite;# Migraine;# Anxiety
5HT2A
5HT 3
5HT1B/1D
5HT 1A
Miscellaneous (Pharmacology)