Presentation on theme: "CNS Stimulants 1. Analeptics stimulate autonomic system (respiratory and circulation) 2. Methylxanthines (caffeine, theobromate and theophylline) 3. Central."— Presentation transcript:
1CNS Stimulants1. Analeptics stimulate autonomic system (respiratory and circulation)2. Methylxanthines (caffeine, theobromate and theophylline)3. Central sympathomimetics agentsAnalepticsProvigil (Modafinil)Atypical 1 norepinephrine receptor stimulantNacrcolepsy, sleep apneaAdverse side effects: nervousness, anxiety and sleeplessness
2Methylxanthines (Caffeine, theophylline and theobromine) CNS stimulation is believed to belinked to adenosine receptorsDopram (Doxapram HCl)Respiratory stimulant, Overdose withCNS depressant, chronic obstructivepulmonary diseases (COPD)and apneas.
3Compound R R’ R”Caffeine CH3 CH3 CH3 Coffee, TeaTheophylline CH3 CH3 H TeaTheobromine H CH3 CH3 CocoaCaffeine is widely used CNS stimulant. It found in brewed coffee, brewed tea andcola beverages. Dosage range for stimulation is 85 to 250 mg. Adverse side effectsinclude restlessness, anxiety and nervousness. At high dose, convulsion may occur.Use to treat migraine and tension headaches (central vasoconstriction)Theophylline has been used as CNS stimulant, used as bronchodilator.Caffeine being more lipophilic than theophylline thus having higher brainconcentrations. Caffeine’s half-life (5 to 8 hours) and theophylline’s half-life (3.5 hours).Mechanism of action: CNS stimulation (antagonize adenosine A1 and A2 receptors).
5Central Sympathomimetics Agents -phenylethylamineStructure Activity Relationship (SAR)Lower alkyl groups adjacent () increases CNS rather than peripheral activityBranching generates a chiral center. The dextro(S) of amphetamine is 10 timesmore potent than levo (R) isomer.Hydroxylation of ring or () carbon decrease activity. PhenylpropanolamineHalogenation (F, Cl, Br) of the aromatic ring decreases activity. Chloroamphetaminehas strong central serotoninergic activity.Methoxy substitution cause dopaminergic activity (D2)N-methylation increases activity (methamphetamine)Mono substitution larger than methyl decrease activityDi-N-methylation decreases activity
9Benzedrine (Amphetamine Sulfate) racemic mixture more cardiovascular effectDexedrine (Dextroamphetamine Sulfate and Dextroamphetamine Phosphate) (IV)mechanism of action involves the release of Norepi to a smaller extent inhibition ofNorepi uptake at postsynaptic cleft (1)Adderall (combination of salts saccharate, sulfate, aspartate)Dextroamphetamine is strongly basic.(S) configuration has fewer cardiovascular effects and 10 times more potent than(R) as CNS stimulant.Systemic acidosis can cause 60 to 70% of the drug to excreted unchanged.-methyl group retards metabolism by MAO. What is the major route ofmetabolism of dextroamphetamine?Uses narcolepsy, Parkinson’s disease, attention deficient disorders (ADD), dieting.
11Desoxyn (Methamphetamine HCl) Very highly abuse drugStreet name “Meth, Ice, or glass”Uses same as amphetamineDidrex (Benzphetamine HCl)A decrease in activity.Maintain Anorexiant activity ( receptor agonist)Tenuate, Tepanil (Diethylpropion HCl)Anorexiant agentPondimin (Fenfluramine hydrochloride)Sedation rather than excitation (serotoninergic)In combination with phentermine (phen-fen)Removed from market because heart valveDamage 1997 (5HT2B)
12Ritalin (Methylphenidate hydrochloride) marketed as racemateIts p-hydroxy metabolite blocks Norepireuptake and acts as postsynaptic agonist.In the stomach the protonate form isresistant hydrolysis.Uses Narcolepsy orattention deficit disorder (ADD).PemolineRequires 3 to 4 weeks afteradministration to elicit an effect.Delay relayed to increase indopamine synthesis.Trade name Cyclert discontinuedLiver toxicity