MIDTERM 03 - CNS Stimulants Flashcards
Are potent and relatively non-selective CNS stimulants; convulsive dose lies near their analeptic dose
Traditional analeptics
Picrotoxinin and pentylenetetrazole are examples of __________
Traditional analeptics
Are more selective CNS stimulants
Newer agents
Modafinil and doxapram are examples of __________
Newer agents
An active ingredient of picrotoxin; used for determining mechanisms of action of sedatives (Examples of traditional analeptics)
Picrotoxinin
__________ moiety is mandatory for the activity of picrotoxinin, with the 2-propenyl group assisting
Hydroxylactonyl
MOA of picrotoxinin
GABA-A receptor antagonist
Acts as a convulsant; used as a laboratory tool in determining potencies of potential anticonvulsant drugs in experimental animals (Examples of traditional analeptics0
Pentylenetetrazole
MOA of pentylenetetrazole
GABA-A receptor antagonist
Used to treat daytime sleepiness in narcolepsy patients (Examples of newer agent analeptics)
Modafinil
MOA of modafinil
Atypical α1-norepinephrine (NE) receptor stimulant
Used as respiratory stimulant; acts on peripheral carotid chemoreceptors (Examples of newer agent analeptics)
Doxapram
3 examples of naturally occurring methylxanthines (CTT)
Caffeine, Theophylline, Theobromine
Also known as 1,3,7-trimethylxanthine (Examples of methylxanthines)
Caffeine
Also known as 1,3-dimethylxanthine (Examples of methylxanthines)
Theophylline
Also known as 3,7-dimethylxanthine (Examples of methylxanthines)
Theobromine
Methylxanthines are __________ inhibitors
Phosphodiesterase
Methylxanthines act as __________ receptor antagonists
Adenosine
Are agents that are also known as psychomotor stimulants
Central sympathomimetic agents
Central sympathomimetic agents have a __________ moiety
β-phenethylamine
Branching with lower alkyl groups on the carbon atom adjacent to the amino nitrogen __________ CNS rather than peripheral activity (SAR of central sympathomimetic agents)
Increases
Hydroxylation of the ring or β-carbon (to the nitrogen) __________ activity, largely by decreasing the ability to cross the BBB (SAR of central sympathomimetic agents)
Decreases
Halogenation of the aromatic ring __________ sympathomimetic activity (SAR of central sympathomimetic agents)
Decreases
Methoxyl substitution on the ring tends to produce __________ agents (SAR of central sympathomimetic agents)
Psychotomimetic
N-methylation __________ activity (SAR of central sympathomimetic agents)
Increases
Di-N-methylation __________ activity (SAR of central sympathomimetic agents)
Decreases
Mono-N substituents larger than methyl __________ excitatory properties (SAR of central sympathomimetic agents)
Decrease
A racemic mixture that has a higher proportion of cardiovascular effects than the dextro isomer (Examples of central sympathomimetic agents)
Amphetamine sulfate
In dextroamphetamine sulfate, the dextrorotatory isomer has the __________ and fewer cardiovascular effects (Examples of central sympathomimetic agents)
S-configuration
Has a very high abuse potential; more marked central and less peripheral action than dextroamphetamine (Examples of central sympathomimetic agents)
Methamphetamine hydrochloride (Shabu)
__________ are also known as appetite suppressants (Examples of central sympathomimetic agents)
Anorexiants
Phentermine HCl, benzphetamine HCl, and phendimetrazine tartrate are examples of __________ (Examples of central sympathomimetic agents)
Anorexiants
Tends to produce sedation rather than excitation; is an anorexiant (Examples of central sympathomimetic agents)
Fenfluramine hydrochloride
Uptake inhibitor of NE and 5-HT; an antidepressant and anorexiant drug (Examples of central sympathomimetic agents)
Sibutramine
Indications include narcolepsy and ADHD (Examples of central sympathomimetic agents)
Methylphenidate hydrochloride
Increases the rate of synthesis of DA (Examples of central sympathomimetic agents)
Pemoline
Depression is caused by __________ serotonin, norepinephrine, and dopamine (Examples of central sympathomimetic agents)
Low/Decreased
Selective and reversible inhibitor of MAO-A; an antidepressant without producing hypertensive crises (Examples of monoamine oxidase inhibitors)
Moclobemide
Selective and irreversible inhibitor of MAO-B; has value in treating Parkinson diseases (Examples of monoamine oxidase inhibitors) (SR)
Selegiline, Rasagiline
Nonselective and irreversible inhibitor of MAO-A and MAO-B; was used for its hypotensive action (Examples of monoamine oxidase inhibitors)
Pargyline
Nonselective and irreversible inhibitor of MAO-A and MAO-B (Examples of monoamine oxidase inhibitors) (PIT)
Phenelzine, Isocarboxazid, Tranylcypromine
__________ undergoes isosteric replacement of phenothiazines’ “S” with a “C-C” isostere
Tricyclic antidepressants
Prototype of tricyclic antidepressants
Imipramine
__________ contains an iminodibenzyl ring (Types of tricyclic antidepressants)
Dihydrodibenzazepine
Tricyclic antidepressants contain a __________ ring arrangement in which the central seven-membered ring is either carbocyclic or heterocyclic, and saturated or unsaturated, which is fused to two phenyl rings (SAR of tricyclic antidepressants)
6-7-6
The side chain may be attached to any one of the atoms in the central 7-membered ring, but it must be __________ carbon atoms, either saturated or unsaturated, and have a terminal amine group (SAR of tricyclic antidepressants)
3
Substituting a halogen or cyano group into the __________-position of the dihydrodibenzazepine ring enhanced preferential affinity for SERT (SAR of tricyclic antidepressants)
3
__________ amines are sedatives (SAR of tricyclic antidepressants)
Tertiary
__________ amines are stimulants (SAR of tricyclic antidepressants)
Secondary
__________ amines have more affinity for inhibiting 5-HT reuptake (SAR of tricyclic antidepressants)
Tertiary
__________ amines have more affinity for inhibiting NE uptake (SAR of tricyclic antidepressants)
Secondary
__________ amines have higher anti-HAM side effects (SAR of tricyclic antidepressants)
Tertiary
Tertiary amines block __________ receptors, causing orthostatic hypotension (SAR of tricyclic antidepressants)
α1 adrenergic
Tertiary amines block __________ receptors, causing dry mouth, constipation, urinary retention, and blurred vision (SAR of tricyclic antidepressants)
Muscarinic
Tertiary amines block __________ receptors, causing weight gain and sedation (SAR of tricyclic antidepressants)
Histaminic
__________ are drugs that differ from the tricyclics, in that the tricyclic system has been taken apart in the center
Selective serotonin reuptake inhibitors (SSRIs)
By breaking up the tricyclic system (ex. in SSRIs), it gives compounds with __________ anticholinergic effects
Diminished
Fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram are examples of __________
Selective serotonin reuptake inhibitors (SSRIs)
Nisoxetine, reboxetine, and venlafaxine are examples of __________
Serotonin-norepinephrine reuptake inhibitors (SNRI)
Selective serotoninergic reuptake inhibitors and 5-HT2A antagonists such as trazodone and nefazodone are also used as __________
Hypnotics
Has anxiolytic and antidepressant activities (Examples of 5-HT1A agonists and partial agonists)
Buspirone
Its MOA is increased NE release via α2-NE receptor antagonism (Examples of α2 Antagonists)
Mirtazapine
Its MOA is block of DA reuptake via the dopamine transporter (Examples of miscellaneous antidepressants)
Bupropion
It has structural resemblance to the central neurotransmitter, serotonin/5-HT; examples include dimethyltryptamine, psilocybin, and psilocin (Examples of 1β-arylamino hallucinogens)
Indolethylamines
Has a structural resemblance to NE and DA; examples include mescaline, DOM/STP, MDA, and ecstasy (Examples of 1β-arylamino hallucinogens)
2-Phenylethylamines
Has marked effects on serotoninergic and dopaminergic neurons; possesses both indolethylamine and phenylethylamine moiety (Examples of 1β-arylamino hallucinogens)
(+)-Lysergic acid diethylamide (LSD)
Was introduced as a dissociative anesthetic for animals; its close structural relative is ketamine (Examples of dissociative agents)
Phenycyclidine
A psychotomimetic and drug of abuse; a potent DA reuptake blocker (Examples of euphoriant-stimulant)
Cocaine
A phenolic OH is required for activity; binds to cannabinoid receptors, CB1 and CB2 (Examples of depressant-intoxicant)
Δ1-Tetrahydrocannabinol/Δ9-THC
Cannabinoid receptor responsible for CNS actions
CB1
Cannabinoid receptor responsible for immune tissues
CB2