Veterinary Neuropharmacology

NATURAL ALKALOIDS

 Atropine

• Atropine is a racemic mixture of dl-hyoscyamine. It is a tertiary amine alkaloid obtained from the plants Atropa belladonna (deadly night shade plant) and Datura stromanium (thorn apple or jimson weed). Belladona plant also contains two more alkaloids in addition to atropine hyoscyamine and hyoscine.
• Atropine and related antimuscarine drugs competitively antagonize Ach and other muscarinic agonist at all the muscarinic receptors. High doses may also block nicotinic receptors in autonomic ganglia and neuromuscular junctions
• Being competitive in nature, atropine antagonism at muscarinic receptors can be overcome by increasing the concentration of Ach either directly or indirectly by administering anticholinesterase drugs.
• Atropine is more effective in blocking responses to exogenously administered cholinergic agonists than those produced by stimulation of cholinergic nervous system.

Pharmacological Effects

• Effects produced by atropine are opposite to those produced by parasympathetic stimulation or those produced by cholinergic agonists. Due to the heterogeneity of muscarinic receptors, the pharmacological effects of atropine are dose related.
• Salivary and sweat gland secretions are quite susceptible to small doses of atropine, pupil and heart are affected by modest systemic doses and high doses are required for producing GI and urinary tracts. Inhibition of GI secretions require even higher doses of atropine

Cardiovascular systems

• Heart
  • Effects of atropine on heart are dose dependent. At low doses or in initial stages atropine produces transient bradycardia.
  • This attributed to blockade of M₁-muscarinic auto receptors on vagal nerve endings, which results increased vagal discharges of Ach.
  • At normal dose or after initial bradycardia atropine produces tachycardia due to blockade of M₂ receptors on SA node, through which vagal tone decreases heart rate.
  • Atropine shortens the refractory period of AV node and facilitates AV conduction

Blood pressure

• Since vascular smooth muscles do not receive parasymapathetic innervations, cholinergic impulses are not involved in the maintenance of vascular tone.
• Thus atropine alone has no significant effect on BP. How ever atropine will block the sharp drop in BP produced by cholinergic agonists.
• Atropine also potentiates the pressor effect of adrenergic and nor adrenergic by blocking the cardio inhibiting effects of vagus.

Smooth muscles

• All nonvascular smooth muscles that receive parasympathetic nerve innervations are relaxed by atropine due to blockade of M₃ muscarinic receptors.

Gastrointestinal tract

• Atropine relaxes the GI smooth muscles by inhibiting the contractile responses produced by endogenous Ach.
• It reduces tone and motility of gut (results in increased gastric emptying time) and causes closure of sphincter. Amplitude and frequency of peristalsis is also, reduced resulting in antispasmodic or spasmolytic effect.

Respiratory System

• Atropine relaxes the bronchioles that are constricted due to excessive cholinergic activity.
• However it is not useful in bronchial asthma, where the bronchospasm is mediated by spasmogens other than Ach

Urinary tract

• Atropine relaxes ureter and urinary bladder and causes urinary retention. As atropine reduces the tone of ureter it is useful ureteric colic.

Eye

• Atropine causes mydriasis and cycloplegia (inability to focus for near vision) and abolishes light reflexes.
• This results in photophobia and blurred vision. Atropine raises the intraocular pressure in glaucoma patients.
• These effects are produced either by topical or systemic administration

Exocrine glands

• In general atropine reduces all secretions except milk. Atropine markedly decreases sweat, salivary, tracheo bronchial and lachrymal secretions due to M₃ receptor blockade.
• Eyes become dry and swallowing may be difficult. However gastric secretions are not completely inhibited due to involvement of non cholinergic receptors also. Similarly intestinal and bile secretions are not markedly affected.

Body temperature

• Due to inhibition of sweating and stimulation of thermo regulating centre in hypothalamus atropine raises the body temperature.

Central Nervous System

• Therapeutic doses of atropine have minimal effect on CNS but larger doses have stimulant effect.
• Very high doses causes hallucinations and disorientations in humans,  mania and excitement in domestic animals, which is later followed by depression and coma.