Psychomotor & Psychomimetic Stimulants Flashcards
1
Q
What are psychomotor stimulants
A
drugs associated with increased motor output and euphoria
2
Q
What are psychomotor stimulants associated with?
A
Euphoria and increased motor output
Psychomotor stimulants enhance feelings of happiness and contentment while also increasing physical activity.
3
Q
What do psychotomimetic stimulants induce?
A
Psychosis-like states
These stimulants can alter perception of reality, often resembling schizophrenia.
4
Q
Name three examples of psychomotor stimulants.
A
- Amfetamine
- Cocaine
- Caffeine
These drugs have similar effects on the central nervous system.
5
Q
what do psychomotor stimulants do ?
A
effect mental functions and behaviour by acting on CNS
- increase alterness
- increase mood
- increase sense of well-being
- decrease appetite
- decrease fatigue
6
Q
What is the primary neurotransmitter pathway affected by psychomotor stimulants?
A
Central modulatory catecholaminergic pathways
- these pathways involve neurotransmitters like dopamine and noradrenaline
- also on 5HT pathways (not catecholaminergic)
7
Q
what are the periphral effects of psychomotor stimulants and why?
A
e.g. changes in blood pressure
- as taken through peripheral roots
peripheral effects on cardiovascular system
8
Q
What is the medical use of methylphenidate as a psychomotor stimulant?
A
Treatment of ADHD
9
Q
What was a historical use of psychomotor stimulants in the military?
A
To maintain alertness over long periods
Benzedrine was used by military personnel to enhance attention during prolonged tasks.
10
Q
potential harms of psychomotor stimulants:
A
- abuse potential
- prolonged use is neurotoxic
- repeated use can lead to tolerance and dependence
11
Q
Fill in the blank: Psychomotor stimulants act on the _______ system.
A
Central nervous system
They have significant effects primarily on brain functions.
12
Q
What is the chemical structure of amfetamine characterized by?
A
A small ring structure and proximal amine groups
amine = R-NH2
13
Q
What is the role of the noradrenergic pathway in the brain?
A
- in CNS
- Maintain arousal and attention
This pathway has widespread connections throughout the central nervous system.
14
Q
what are the key regions that produce NA in the brain ?
A
- LC: locus coeruleus
- LTA: lateral tegmental area
15
Q
where does the locus coeruleus project to ?
A
- cerebelum (movement)
- limbic structures (hypothalamus and amygdala)
- cerebral cortex
16
Q
where does early AD pathology happen in the brain ?
A
noradrenergic LC
which may lead to potential memory issues in AD
17
Q
noradrenergic pathway + label
A
- lC
-LTA - NTS
- SC
- Am
- Hip
-Hyp
-Th
-Str
-Sep
note where red pathway goes
18
Q
where does the LTA project to ?
A
descending projections through spinal cord
19
Q
What can prolonged use of psychomotor stimulants lead to in terms of brain health?
A
Neurotoxicity
High doses or long-term use can damage brain regions controlling cardiovascular functions.
20
Q
What neurotransmitter is associated with mood and sleep regulation?
A
Serotonin (5-HT)
Serotonin is crucial for various brain functions, including mood stabilization.
21
Q
What is the common effect of psychomotor stimulants on mental functions?
A
Increased alertness and mood
They often enhance feelings of happiness and contentment.
22
Q
Name the three key pathways associated with dopamine.
A
- Nigrostriatal pathway
- Mesolimbic pathway
- Mesocortical pathway
Each pathway is involved in different brain functions and associated with various neurological conditions.
23
Q
dopaminergic pathways in the brain - labeled diagram
A
- mescocortical
- nigrostriatal
- mesolimbic
- tuberohypophseal
important labels :
- SN
- Str
- VTA
- NAc
24
Q
What does the nigrostriatal pathway connect?
A
Substantia nigra to the striatum
This pathway is crucial for motor control and is affected in Parkinson’s disease.
25
what is the name for the serotonin pathway?
Tryptaminergic (5HT)
26
what is the tryptaminergic pathway involved in ?
- widespread in CNS
- frontal control of mood
## Footnote
through lots of different limbic sites important in learning and memory and cerebral cortex and thalamus and striatum
27
what is the main site of serotonin production the the mammalian CNS ?
Raphe Nuclei
## Footnote
which is in medulla
28
Tryptaminergic pathway labeled diagram
- Raphe Nuclei
- Am
-Hip
- Sep
-Str
- Hyp
- C
| remembr red labels
29
What is the Nigrostriatal pathway ?
substantia nigra (SN) -> dorsal striatum
30
what is the nigrostriatal pathway involved in ?
## Footnote
Dopamine pathway
- motor function
- implicated area of degeneration in PD
31
what is the mesolimbic pathway ?
## Footnote
DOpamine
ventral tegmenal area (VTA) -> nucleus accumbens (NAc)
32
what is the mesolimbic pathway involved in ?
reward and addiction
33
what is the mesocortical pathway ?
ventral tegmental area (VTA) -> medial prefrontal cortex
34
what is the mesocortical pathway involved in ?
- congitive function (attention, motivation, reward sensitivity)
- implicated in schizophrenia
35
what is over production of dopamine in the nucleus accumbens and reduction in dopamine singalling in medial prefrontal cortex associated with ?
hallucinations
## Footnote
cognitive deficit
36
what is the Tuberohypophyseal pathway associated with ?
inhibits prolactin release
37
what are dopamine pathways involved in ?
- attention
- reward
- addiction
- arousal/wakefulness
- memory formation
- memory consolidation
- movement control
38
dopaminergic pathways in rodents
similar to humans
39
catecholaminergic synapse - labelled diagram for DA and NE
40
what is the metabolic pathway through which DA and NE re produced ?
- L-tyrosine (via Tyrosine hydroxlase) to L-DOPA
- L-DOPA (via DOPA decarboxlase) to Dopamine
- Dopamine (via phnyleethanolamine methytransferase) to norepinepherine (adrenaline)
41
what can we stain for to figure out if a neuron is dopaminegic or not ?
tyrosine hydroxylase
42
what does VMAT do
- vesicular monoamine transporter
- packages neurotransmitter in to vesicles
43
reuptake of dopmaine ?
DAT - dopamine transporter on presynaptic nerve terminal
## Footnote
turns off dopamine signal
44
what does MAO do ?
monomaine oxidase
- degradation of dopamine (and NA) and allow it to be recycled into the metabolic pathway
45
Mechanism of action for amfetamine ?
- increases availability of NE/DA in synapse
46
how do amfetamines increase NE/DA at synapse ?
1. outcompete NET/DAT which blocks reuptake of NE/DA : increases synaptic levels
2. act on internal transporters e.g. VMAT: increased NE/DA in terminal
3. at high concentration can inhibit MAO: increases cytosolic NE/DA
## Footnote
4. result of all of this is increased internal conc. which revrses function of transporters
47
what does amfetamines increasing internal NE/DA do ?
reverses remaining action of NET/DAT
- moves opposite way into synaptic cleft and inhibits movement out of synaptic cleft into cell
48
behavioural effects of increasing DA or NE in CNS
- locomotor stimulation
- euphoria
- insomnia
- increased stamina
- appetite effect
49
where does locomotor stimulation occur ?
nigrostriatal system
50
peripheral affects of amfetamines ?
- raised BP
- inhibition of gastris mobility
51
what does amfetamine do on mental performance ?
- better for simple tasks
- impaired on complex tasks
52
adverse effects of amfetamines
- anxiety
- irritability
- restlessness
- high doses: paranoia and panic
53
narcolepsy
disabling state
- falling asleep at unpredicatable times as arousal systems dysregulated
54
4 subtypes of narcolepsy
- daytime sleepiness (EDS)
- cataplexy
- sleep paralysis
- hyponopompic (before you wake up)/hypnagogic (when falling asleep) hallucinations
55
example of an a drug used to treat narcolepsy
modafinil (provigil)
## Footnote
not an amfetamine but is a stimulant
56
what does modafinil do ?
inhibits amine reuptake
57
what neurons does modafinil affect ?
orexin neurons which are important in the onset of sleep
58
what does modafinil not affect ?
MAO as structurally different to amfetamine
59
side effects of modafinil
nausea, headache, insomnia
## Footnote
less risk of dependence compared to ampfetamine
60
what is ADHD characterised by
low attention span and hyperactivity
61
what do amfetamine like drugs do for ADHD ?
reduce impulsivity and improve attention
62
what is an example of a stimulant used to treat ADHD ?
methylphenidate (ritalin)
| potential for abuse/ mechanism unkown
## Footnote
amfetamine like drug but is not an amfetamine
63
what is a non-stimulant medication used to treat ADHD ?
atomoxetine
64
what are the mechanisms of action of atomoxetine ?
selective NE reuptake inhibitor
## Footnote
NET
65
how does non-stimulant atomoxetine compare to amfetamine ?
amfetamine is not selective, atomoxetine is
66
what is a benefit of atomoxetine ?
it can be used in combination with methylphenidate
67
action of modafinil in ADHD
- selective amine inhibitor at A adrenoreceptors and 5HT/Glu/Histamine relase and inhibition of GABA release
68
what does repeated use of amfetamines over short periods potentially lead to ?
amfetamine psychosis
69
what is amfetamine psychosis and how does this happen ?
- acute schizophrenia
- overactivation of DA signals into striatum
70
what kind of behvaiours can use of amfetamines lead to ?
repetitive and stereotypical behaviours
| 'punding' e.g. scratching or OCD like symptoms
## Footnote
probably more related to serotonin
71
what are stereotypical behaviours likely due to ?
overactivation of striatum (serotonergic input)
## Footnote
also linked to OCD
72
what is tolerance in the use of amfetamines ?
a decrease in behavioural response to the drug when used repeatedly
73
what is dependence
we have reduced basal levels of dopamine once we come off the drug
| changes amount of drug needed to get the same response
## Footnote
(withdrawls)
74
what is physiological dependence ?
reward system adjusts to lower DA release, so once off - more amfetamine is needed to replace this
75
what is psychological dependence
persistent 'memory' of euphoria
76
what is cocaine ?
plank alkaloid from coca plant
77
what was cocaine orgionaly used for ?
a tonic for fatigue
78
what are some serious side effects of cocaine ?
cardiovascular effects
79
mechanism of action of cocaine
- on reuptake of NE, DA, 5HT so more in synapse
- blocks Na+ channels
## Footnote
NET/DAT/SERT
80
what can cocaine also be used as and why
a local anaesthetic as it blocks Na+ channels
81
what does nasal adminitration of cocaine lead to ?
- rapidly absorbed
- destroys local tissues via vasoconstriction
- can lead to perforated septum
82
what is the free base of cocaine ?
- prepared from salt
- vaporsies at ~90 degrees C
83
where is the free base of cocaine metabolised ?
in the live
## Footnote
metabolites are measurable in human hair
84
what are the toxic affects of cocaine ?
- acute and chronic cardiovascular effect
e.g. systolic and diastolic dysfunction, arrythmias, atherosclerosis
85
what can taking cocaine during pregnancy do ?
- fetal malformation
- microcephaly if taken during pregancy (smaller head and brain)
86
what do psychomotor stimulants do ?
increase availability of catacholamines such as NE or DA and some for 5-HT at extra-synaptic receptors
87
what is the chemical name of caffeine ?
methylxanthine
88
where is caffine found ?
in the nuts of coca plants
89
what kind of stimulant is caffeine ?
mild CNS stimulant
90
how does caffeine act peripherally ?
as a diuretic on kidneys
91
what is theophylline ?
related compound to caffeine, used for peripheral effects on lung function
92
how does caffeine act ?
- inhibits central adenosine receptors (A1, A2)
- inhibits phosphodiesterase enzymes
93
what does adensoine do ?
modulatory with ATP and results in reduction of CNS activity
## Footnote
and as caffeine inhibits this it acts as a stimulant
94
what does caffeine inhibiting phosphodiesterase enzymes do?
increases local cAMP
95
caffeine in CNS
- no psychomimetic functions (hallucinations) or stereotyped actions
- metnal functions improved at moderate dozes and impaired at higher
96
moderate doze of caffeine
2 cups or 200mg
97
risks of caffeine
- tolerance
- habituation
98
caffeiene as neuroprotective mechanism
benefits the survival of cells in our system
99
neuroprotective actions of caffeine
- as A2 adrenoreceptor
- modulates VMAT-2 expression
100
what does caffienes modulation of VMAT-2 do ?
prevents neurotoxicity and neuronal damage
101
caffeine as a psychomotor stimulant
antagonsim of adenosine receptors A1/2 and inhibits phosphodiesterase enzymes
102
what is pervitin ?
non-perscription brand of metamfetamine (German)
103
why was amfetamine give to british and american pilots in WW2
endurance enhancement
104
benefit of modafinil over other amfetamines
lower abuse and addiciton potential
105
psychotomimetrics
drugs capable of producing psychosis-like effects
- psychedelics or hallucinogenic drugs
106
what do psychotomimetics affect?
perception, thought, mood
107
difference between psychomimetics and psychomotor stimulants
psychomimetics show no psychomotor stimulation and minimal intellectual or memory impairment
108
benefits of psychomimetics
- low autonomic side effects
- little to no dependence or abuse potential
109
LSD
lysergic acid diethlamide
- derived from ergot (cereal plant fungus)
110
where is Mescaline from
drived from mexican peyote cactus
111
where is psilocybin from
mushroom in psilocybe genus
112
LSD as a synthetic drug
- produced by Sandoz Inc.
- in an attempt to make a new version of ergotamine that was less toxic (used to treat migranes)
113
ergotamine
low theraputic index
- effective doze ~ toxic dose
## Footnote
low lcinical benefit
114
phsiological effects of psychotomimetics drugs
- somatic (body)
- perceptual (sense)
- psychic (cognition)
115
where are all psychotomimetics all derived from ?
naturally-occuring compounds
116
what are the clinical benefits of psylocibin ?
can allow new connections to be made and rewire old ones
- only need one dose for theraputic benefits in relation to MDD
- less side effects
117
what are the mechanisms of the pharmacological effects of psychotomimetics ?
- largely through 5HT2A receptors: they act as agonists
118
key area of action for psychotomimetics
cingulate cortex
119
what can activation of 5HT2A receptor via psychomimetics indirectly cause ?
## Footnote
in addition to activity at 5HT2A receptors
may indirectly block glutamate activation of NDMAR
120
what does LSD specifically also activate and what does this do?
5HT1A autoreceptors on 5HT cells of Rapge Nucleus
- slows firing rate and decreases 5HT release
## Footnote
shows push pull mechanism on serotonin mechanisms on the brain / activates in cingulate cortex but reduces in raphe nuclear cells
121
where is mescaline thought to act
5HT2A receptors
122
metabolism of psilocybin
into psilocin
123
where does psilocin act primarily ?
5HT2A receptors
| also at other 5HT receptors
## Footnote
interest for theraputic effects
124
adverse effects of psychotomimetics
- no physical withdrawl symptoms
- 'flashbacks' ~ 3 weeks after one LSD dose evidence of hallucinations continuing
- 'bad trips'
- low potential for 'schizophrenic' attacks
125
chemical name for ecstasy/ MDMA
3,4 -methylenedioxymethamphetamine
126
MDMA effects
- euphoria
- mild hallucinations
127
pharmacological effects of MDMA
- changes in NE
- affect reuptake and breakdown and repackaging
- increased availability in synapse
- increase firing of PSN
128
MDMA and 5HT
- increases 5HT as competitive inhibitior of SERT
## Footnote
similar pharmacological action to some ADs e.g. SSRIs
129
what happens with MDMA at higher doses
release of DA
## Footnote
similar to amfetamine
130
CNS changes via MDMA
- DA
- 5HT
- NE
131
adverse effects of MDMD
sudden illness or death caused by
1. acute hyperthermia
2. excess water intake
3. Heart failure
132
what can acute hyperthermia lead to
muscle damage and renal failure
133
what can excess water intake lead to
- increased ADH production
- excess water ingestion (hyponatraemia)
- dizziness, disorientation, coma, death
134
ADH production
- through HPA axis
- tells body to reduce urinationa and conserves water
135
what is hyponaatraemina
imbalance of sodium and water in the body,
causing excess water in extracellular space, cells take up too much water and cells swell and can burst
136
MDMA and heart failure
in indivudals with undiagnosed cardiac conditions
137
Binging on MDMA
increases psychostimulant response, dopamine activation can be stimulate the more you take
138
long lasting effects of MDMA
- depression, axiety, irritability, aggression
- LT effects on memory and congitive functions in heavy users
## Footnote
as effect 5HT levels and transmission
139
what is ketamine
dissociative anaesthetic used in vetinary practice
140
what is Phencyclidine
PCP / angel dust
- ketamine analogue
## Footnote
less available/less used
141
ket & PCP
euphoria, hallucinations, detachment and disorientation
142
PCP in neuropsychiatry
- can cause psychotic episodes and can be used to induce schizophrenic-like states in rodent models
143
what do PCP rodent models show
poor cognitive performance, social memory, social activity
## Footnote
injected over a couple of weeks for schizophrenic model
144
mode of action for ketmaine and PCP
- blocks NMDA receptors for a long duration
- causes disinhibition of inhibitory neurons (promotes excitability)
145
what are NMDA receptors
voltage sensitive Glu-activated ionotropic receptor
- associated with inhibitory neurons
## Footnote
critical in cognition, learning and memory
- modulate excitatory glutamate signal
146
what theory supports the role of Ketamine as an AD?
The Disinhibition Hypothesis
147
The disinhibition Hypothesis
| and diagram
## Footnote
(ketmaine and PCP)
- disrupts excitatory-inhibitory balance
- ketamine acts on GABA-ergic interneurons (inhibitory)
- inhibits GABA-ergic neurons
- changes sodium influx and depolarization of (post-) membrane
- allows more excitation on post synaptic membrane
148
side effects associated with ketamine and PCP
- bladder/urinary defects (cystitis, inflammation, shrinkage)
- hives
- hypotension
- nausea
- seizures
- dangerous in overdose (especially if used in combination with other drugs e.g. alcohol)
149
how do psychotomimetics cause mood changes and hallucinations ?
- actions on central 5HT systems and DA (LSD, psilocybin, mescaline, MDMA)
- actions on central NMDA synapses (ketamine, PCP)
150
what psychotomimetic substance induces ADH production ?
MDMA
151
what is PCP an analogue of ?
ketamine
152
mechanism of action for PCP and ketamine
blok NMDA receptors causing disinhibition of inhibitory neurons - prolonging excitability
153
what is a key peripheral adverse side effect of taking ketamine or PCP
urinary issues
154
Which phenotype(s) suggest that rodents may not be a good model for testing the effects of psilocybin?
- animals do not self-administer
- some effects are hard to objectivley measure in animals e.g. hallucinations
155
St Anthony's Fire
disorder cause by poisoning due to consumption of alkaloids produced by ergot fungus
156
what is another name for St Anthony's Fire
ergotism
157
what are the 2 forms of ergotism ?
- convulsive (sezures, psychosis, itching)
- gangreous (circulation lost in extremities e.g. fingers)
158
what is a powerful property of ergot alkaloids that causes loss of circulation to extermities ?
vasoconstriction
159
where does ergot fungus grow?
cereal crops such as barley and rye, enters food chain through flower and bread
160
what is ergotamine and what di it give rise to?
- ergoline alkaloid
- LSD is dervied from this
161
theraputic properties of ergolines
(vasoconstrictive)
- migraines
- to help induce childbirth
162
what drug is an antagonist at adenosine receptors ?
- caffeine at A1 and A2
## Footnote
also inhibits phosphodiesterase
163
what drug is a selective noradrenaline reuptake inhibitor ?
atomoxetine (more selective for NET over DAT)
## Footnote
cocaine inhibits reuptake of NA, DA, 5HT
methylphenidate and dexamphetamine inhibits both NET and DAT
164
what is NOT a component of the mechanism of amfetamine ?
inhibition of SERT
165
which drug is most likely to produce schizophrenia -like symptoms if taken repeatedly over a short period?
amfetamine
- can causes psychosis or stereotyped behaviours
166
what drug is not self-administered in animal models of drug dependence ?
caffeine
## Footnote
ones that are sel0fadministered indicated produce dependence
167
mechanism of action for modafinil ?
unknown but possibly via DAT inhibition (weak)
168
Which amfetamine derivative exerts its effects primarily through increasing synaptic serotonin concentrations?
MDMA
## Footnote
also inhibits vesicular monoamine transporter, can also cause transporters to run backwards increasing synaptic levels
