WK6-intro to cholinergic synapse/receptors

what is cholinergic

they are neurons secreting ACh

what is muscarine

an alkaloid from the fungus muscaria which could slow the heart

what is atropine

it is an alkaloid from atropa belladonna - which could blocks actions of muscarine

what is the muscarinic receptor

• it is a GPCR activated by ACh

• it has 7 transmembrane structures

• and is signalled via 2nd messengers in the cells

what are 5 muscarinic subtypes

1. M1 - found in CNS, glands & SM - signal through IP3/INCREASCA2+(Gq) & inhibits potassium channels

2. M2- cardiac, so found mainly in the heart- also signal via cAMP (Gi) decrease opening activation of K+ potassium channels

3. M3- found in glands & SM - stimulates (Gq) which signals via IP3 increasing Ca2+

4. M4&M5 - found in CNS - M4 siganl’s through cAMP (decreases by inhibiting adenylate cyclase) M5 - signal via Ips/ increase in Ca2+ (Gq)

what is the term for muscarinic agonist

parasympathomimetics

what is the term for muscarinic antagonist

parasympatholytic

what 6 agonist drugs act at muscarinic agonist

1. acetylcholine

2. carbachol

3. methacholine

4. bethanechol

5. muscarine

6. pilocarpine

what subtype is Xanomeline and what does it do

M1 - used for development of alzheimer’s disease

what is cevimeline subtype & what does it do?

Sjögren’s syndrome to increase salivary and lacrimal secretion & M3 receptor

what are the effects pf muscarinic agonist on cardiovascular

• bradycardia - slow heart rate

• decreases cardiac output

• vasodilation via Nitric oxide

• decreases blood pressure

what are the effects pf muscarinic agonist on smooth muscle

• contraction of SM

• Bladder contraction

• constriction of bronchioles

what are the effects pf muscarinic agonist on eye

• pupil constriction

• constriction of ciliary muscle (accommodation)

• causing decrease intraocular pressure (glaucoma)

what are the effects pf muscarinic agonist on glands

it increase secretion like sweating, lacrimation, salivation, enzymes

what is the clinical use of muscarinic agonist

• for glaucoma, to decrease intraocular pressure is pilocarpine, but not frequently used

• Bethanechol- used very rarely to treat urinary retention

what are muscarinic antagonist

atropine and it is non-selective, which crosses BBB

what are 6 muscarinic antagonist

1. tiotropium - asthma

2. ipratropium - asthma

3. hyoscine - motion sickness

4. tropicamide - ophthalmology

5. pirenzepine -M1

6. darifenacin -M3 - urinary

what are the effects of muscarinic antagonist on cardiovascular

Tachycardia (inhibits vagal tone, but responses to exercise are unaffected) – Blood pressure unchanged

what are the effects of muscarinic antagonist on smooth muscle (relaxation)

GIT –motility inhibited–

Urinary tract (bladder) – relaxation–

Bronchial – relaxation - bronchodilation

what are the effects of muscarinic antagonist on eye

Dilation of pupil – no light reflex–

Relaxation of ciliary muscle – loss of accommodation

what are the effects of muscarinic antagonist on glands

Inhibition of secretions

• Salivary (dry mouth)

• Lacrimal (dry eye)

• Sweat glands (dry skin)

• Bronchial

Side effects of muscarinic antagonists

Dry mouth

• Dry skin

• Reduced bronchial secretions

• Tachycardia, palpitations, arrhythmias

Constipation

• Urinary urgency and retention