CNS Stimulants PDF

CNS stimulants Dr Mohammed Shoaib Patel M Pharm (Pharmacology) PhD CNS stimulations: Primary action of diverse group of phamacological agents- adverse effect associated with many drugs Behavioral Manifestations of CNS Stimulation Mild elevation in alertness, decrease in drowsiness and lessening...

CNS stimulants Dr Mohammed Shoaib Patel M Pharm (Pharmacology) PhD CNS stimulations: Primary action of diverse group of phamacological agents- adverse effect associated with many drugs Behavioral Manifestations of CNS Stimulation Mild elevation in alertness, decrease in drowsiness and lessening of fatigue (Analeptic Effect) Increased nervousness and anxiety -convulsions CNS Stimulants Stimulant are drugs that temporarily increase alertness and awareness. They usually have increased side-effects with increased effectiveness, and the more powerful drugs are therefore often prescription medicines or illegal drugs. Stimulants increase the activity of either the sympathetic system, central nervous system or both. Some stimulants produce a sense of euphoria, in particular the stimulants which exert influence on the CNS. Stimulants are used therapeutically * to increase or maintain alertness * to counteract fatigue in situations where sleep is not practical (e.g. while operating vehicles) * to counteract abnormal states that diminish alertness consciousness (such as in narcolepsy) * to promote weight loss (Anorectics) as well as to enhance the ability to concentrate in people diagnosed with attentional disruptions CNS Stimulation Imbalance between inhibitory and excitatory processes as in the brain. This hyper-excitability of neurons results from: potentiation or enhancement of excitatory neurotransmission (e.g. amphetamine) depression or antagonism of inhibitory transmission (e.g. Strychnine) presynaptic control of neurotransmitter release (e.g. picrotoxin) Classification 1. Psychomotor stimulants (Central Stimulant Sympathomimetics) β–Phenylethylamine derivatives: Amphetamines and related drugs Methylxanthines: Caffeine, Theophylline, Theobromine, Aminophylline, Etophylline, Methylphenidate 2. Analeptics (Respiratory stimulants): Doxapram, Nikethamide 3. Convulsants: Strychnine , Picrtoxin , Pentylenetetrazol 4.Pshychotomimetic Drugs: Hallucinogenic drugs Lysergic acid diethyl amide, Phencyclidine, Cannabis Psychedelic drugs: group of compounds that induce visual and auditory hallucinations. The analeptics stimulate respiration in subconvulsive doses, but margin of safety is narrow. The patients may get convulsions while still in coma. Mechanical support to respiration and other measures to improve circulation are more effective and safe.  1. Psychomotor stimulants β – Phenylethylamine derivatives (Central Stimulant Sympathomimetics) H CH3 R1 N R3 R2 R Name R R1 R2 R3 Amphetamine H H H H Methamphetamine CH3 H H H phentermine H H CH3 H Benzphetamine -CH2C6H5 H H CH3 Mechanism of action They inhibit reuptake mechanisms for several biogenic amines. They enhance neuronal release of catecholamines. They stimulate α - adrenergic receptor and inhibit mono amino oxidase is higher concentration. Uses : Used for Weight Loss (Anorectics) Methylphenidate ,( Piperidine derivative) C6H5 Na CN C6H5 N Cl H N CN Cyanophenylmethylsodium H2SO4/NH3 CH3OH C6H5 C6H5 C6H5 Catalytic [H] N COOCH3 HCl N CONH2 N COOCH3 H.HCl Methylpenidate HCl MOI: Block NE uptake also act as post synaptic agonist Methylxanthines (Psychomotor stimulant) O R1 R N Thea sinensis- tea N Coffee- Theobroma cacao O N N R R1 Caf f eine CH3 CH3 Theophylline CH3 H Theobromine H CH3 Etof ylline CH3 CH2CH2OH Mechanism Actions of methylxanthines They block adenosine A1-receptors. Adenosine acts as a local mediators in CNS, CVS and other organs. Adenosine contracts bronchial muscles, dilates cerebral blood vessels, and inhibits gastric secretions. Methylxanthines inhibit phosphodiestarease which degrades intracelullarly cAMP. Theophylline-containing preparations enhance cAMP accumulation. It results in bronchodilation and cardiac stimulation. Uses : Caffeine – Treatment of migraine along with ergotamine also used along with analgesics Antiasthmatic (bronchodilatation) effect of theophylline is more potent then those of caffeine. Slow but sustained dose related bronchodilatation is produced and vital capacity is increased. Eg. Aminophylline- soluble complex of  Analeptics (Respiratory stimulants) Doxapram, Nikethamide Doxapram Direct acting stimulants Increase nueronal excitability by decreasing neuronal recovery time or by increasing responsiveness to excitatory neurotransmitters. Doxapram Claimed to be a specific respiratory stimulant and to be useful in treatment of drug induced respiratory depression. Supportive treatment is better. Sometimes used in anesthesia. Nikethamide : in excessive CNS depression, Respiratory depression 3. Convulsants Strychnine is an alkaloid from seeds of Strychnos nux vomica. It acts by blocking post-synaptic inhibition produced by the inhi- bitory transmitter glycine. Strychnine is a potent convulsant. The convulsions are tonic-clonic and symmetrical. There are no valid use of strychnine now. Picrtoxin is obtained from plant Anamirta cocculus. It produces asymmetrical clonic convulsions by blocking inhibition mediated through GABA, block chloride channels. Picrotoxin has no therapeutic indication now. Pentylenetetrazol is a powerful CNS stimulants, acting by direct depolarization of central neurones. Also a GABA  Convulsants Strychnine Picrtoxin 1,5- pentamethylene tetrazole Phychotomimetic Drugs (Hallucinogenic drugs) Psychedelic drugs - Lysergic acid diethyl amide, Phencyclidine, Cannabis indoloquinoline Phencyclidine LSD in CNS acts as 5-HT receptor agonist THC- Bind to specific cannabinoid (CB) receptors located in various brain areas. Phencyclidine- blocks NMDA- type glutamate receptors Benzochromen N-methyl-D-Aspartate (NMDA) recept Thanks