PHARMACOLOGY 2 & THERAPEUTICS LABORATORY

Experiment 4. DRUGS AFFECTNG CNS

B. CNS STIMULANTS

Two Groups of Drugs that act primarily o stimulate CNS

1. Psychomotor stimulants – cause excitement and euphoria, decrease feeling of

fatigue, and increase motor activity.
A. Methylxanthines – includes theophylline found in tea, theobromine in cocoa,
caffeine (most widely consumed stimulant in the world).
MOA – translocation of extracellular calcium, increase cyclic adenosine
monophosphate (cAMP) ad cGMP caused by inhibition of phosphodiesterase and
blockade of adenosine receptors
B. Nicotine – active ingredient in tobacco.
MOA – causes ganglionic stimulation by depolarization. Increase dose causes
ganglionic blockade.
C. Cocaine – tropane alkaloid that is obtained from the leaves of the Erythroxylum
coca plant.
MOA – blockade of norepinephrine, serotonin and dopamine reuptake into the
presynaptic terminal form which these transmitters are released.
D. Amphetamine – behavioural effect are similar to cocaine.
MOA – release intracellular stores of catecholamines. Also blocks MAO.
2. Psychotomimetic drugs or hallucinogens produce profound changes in thought
patterns and mood, with little effect on brainstem and spinal cord.
A. LSD – serotonin (5-HT) agonist activity at presynaptic receptors in the midbrain.
B. PCP – “angel dust” inhibits re-uptake of dopamine, 5-HT, and NE. An analog of
ketamine (anaesthetic, used in veterinary med).
C. THC – aka dronabinol, the main alkaloid found in marijuana.

Naturally occurring plant constituents that can stimulate CNS.

Ex.
Strychnine – Poison nut (Nux vomica)
Cathinone – Khat (Catha edulis) an amphetamine-like stimulant which is said to
cause excitement, loss of appetite, and euphoria.
Caffeine - (tea, coffee, chocolates)
Ephedrine - genus Ephedra

HLC Page 1
 Experiment 5. DRUGS AFFECTNG ANS

A. Chlolinergic Agonists and Antagonists

Direct Acting Cholinergic Agonists

1. Acetlychloline
2. Bethanicol
3. Carbachol
4. Pilocarpine

MOA of Cholinomimetic Agents

1st Ach is released from parasympathetic nerves activates muscarinic receptors on

effector cells to alter organ function directly.

2nd Ach released interacts with muscarinic receptor on nerve terminals to inhibit the
release of their neurotransmitter. Ach release and circulating muscarinic agonists
indirectly alter organ function by modulating the effects on parasympathetic and
sympathetic NS.

Antimuscarinic Agents

1. Atropine
2. Ipratropium
3. Scopolamine

Atropine
MOA – causes reversible (surmountable) blockade of cholinomimetic actions at muscarinic
receptors. When atropine binds to the muscarinic receptor, it prevents actions such as the
release of inositol trisphosphate (IP3) and the inhibition of adenylyl cyclase that are caused by
muscarinic agonists.

Therapeutic Uses
Pilocarpine
- drug of choice in the emergy lowering of intraocular pressure of both narrow
angle (closed-angle) and wide-angle (open-agle) glaucoma.
- effective in opening the trabernacular meshwork around Schlemm’s canal,
causing immediate drop in intraocular pressure as a result of increase drainage
of aqueous humor.
miosis - constriction of the pupil of the eye, resulting from a normal response to an increase in
light or caused by certain drugs or pathological conditions.

Atropine
- mydriatic, cycloplegic – permits measurement of refractive errors without
interference by the accommodative capacity of eye.

HLC Page 2
 mydriasis – dilation of the pupil of the eye caused by contraction of the dilator
muscle of the iris, decrease in light, action of drug.
cycloplegia - paralysis of the ciliary muscles of the eye that results in the loss of
visual accommodation.
- Antispasmodic – relax GIT & bladder.
- Antidote for cholinergic agonist. Tx of organophosphate overdose and mushroom
poisoning.
- Antisecretory agent – blocks secretion in upper and lower respiratory tracts prior
to surgery.

Natural sources of the alkaloids Atropine and Pilocarpine.

Atropine (isomer Hyoscyamine)

- found in Solanaceae family
Atropa belladonna (deadly nightshade)
Datura stramonium (Jamestown weed, sacred datura, thorn apple)
Hyoscyamus niger (henbane)
Mandragora officinarum (mandrake)

Pilocarpine
- Rutaceae family , genus Pilocarpus, (commion name Jaborandi )
Pilocarpus pennatifolius (South American shrub)

Based on MOA of Atropine and Pilocarpine, are these drugs addicting? Why?

No,

Theories of Drug Addiction

McKim (1997) describes three models of why people become addicted to drugs, or engage
in substance abuse.

1. the disease model

2. the physical dependency model - after repeated exposure to certain drugs,
withdrawal symptoms appear if the drug is discontinued.
3. the positive reinforcement model - reinforcers are thought to increase the effect of
dopamine at receptors in the mesolimbic system which originates in the ventral
tegmental area and terminates in the nucleus accumbens .

HLC Page 3
 References:

1. Katzung, B. (2006). Basic Clinical Pharmacology. (10th ed.). McGraw-Hill

Professional.
2. Mycek, M., Harvey, R., Champe, P. (1997). Lippincott’s Illustrated Reviews:
Pharmacology. (2nd ed.). Lippincott-Raven Publishers, Inc.
3. Nodine, J., Siegler, P. (1964) Animal and Clinical Pharmacologic Techniques in Drug
Evaluation. Chicago: Year Book Medical Publishers, Inc.
4. University of Plymouth, Department of Psychology Online Resource Drug Addiction.
Retrieved August 12, 2011 from
http://www.flyfishingdevon.co.uk/salmon/year3/psy337DrugAddiction/theorydrugadz
diction.htm

HLC Page 4