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Understanding Intrinsic Activity: The Key to Effective Medication Prescribing · Pearls and Prep

• 0:05
  Welcome
• 0:05
  back,
• 0:06
  my
• 0:06
  friends,
• 0:06
  to
• 0:07
  another
• 0:07
  episode
• 0:07
  of
• 0:07
  Pearls
• 0:08
  and
• 0:09
  Prep.
• 0:09
  It's
• 0:10
  npz.
• 0:11
  Here,
• 0:11
  your
• 0:12
  preceptor
• 0:13
  in
• 0:13
  your
• 0:13
  pocket,
• 0:14
  gonna
• 0:15
  guide
• 0:15
  you
• 0:15
  through
• 0:17
  a
• 0:17
  little
• 0:17
  something
• 0:18
  called
• 0:18
  intrinsic
• 0:19
  activity.
• 0:20
  That
• 0:21
  is
• 0:21
  a
• 0:22
  medication's
• 0:22
  ability
• 0:23
  to
• 0:23
  activate
• 0:24
  a
• 0:24
  receptor
• 0:25
  upon
• 0:25
  binding
• 0:26
  to
• 0:26
  produce
• 0:27
  a
• 0:27
  cellular
• 0:28
  response.
• 0:29
  And
• 0:29
  that,
• 0:29
  my
• 0:30
  friends,
• 0:30
  is
• 0:30
  very
• 0:31
  important.
• 0:31
  We've
• 0:32
  talked
• 0:32
  about
• 0:32
  affinity
• 0:33
  in
• 0:34
  the
• 0:34
  last
• 0:34
  couple
• 0:34
  episodes.
• 0:35
  We
• 0:35
  talked
• 0:35
  about
• 0:36
  occupancy,
• 0:36
  the
• 0:37
  things
• 0:37
  that
• 0:37
  influence
• 0:38
  occupancy,
• 0:39
  the
• 0:39
  things
• 0:39
  that
• 0:39
  influence
• 0:40
  affinity,
• 0:40
  what
• 0:41
  affinity
• 0:41
  is.
• 0:42
  Highly
• 0:42
  encourage
• 0:43
  you
• 0:43
  to
• 0:43
  go
• 0:43
  look
• 0:43
  at
• 0:43
  those
• 0:44
  before
• 0:44
  you
• 0:44
  listen
• 0:45
  to
• 0:45
  this
• 0:45
  episode,
• 0:46
  because
• 0:46
  it's
• 0:46
  all
• 0:46
  tied
• 0:47
  together
• 0:47
  very
• 0:48
  neatly
• 0:49
  and
• 0:50
  beautifully.
• 0:50
  So
• 0:51
  when
• 0:51
  you
• 0:51
  prescribe
• 0:51
  a
• 0:52
  medication,
• 0:52
  it
• 0:53
  helps
• 0:53
  to
• 0:53
  know
• 0:53
  the
• 0:53
  mechanism
• 0:54
  of
• 0:54
  action.
• 0:54
  And
• 0:54
  we're
• 0:54
  not
• 0:55
  gonna
• 0:55
  go
• 0:55
  through
• 0:55
  all
• 0:55
  the
• 0:56
  different
• 0:56
  mechanisms
• 0:56
  of
• 0:57
  action,
• 0:57
  but
• 0:57
  it
• 0:58
  really
• 0:58
  helps
• 0:58
  for
• 0:59
  you
• 0:59
  to
• 0:59
  understand
• 1:00
  that
• 1:00
  there's
• 1:00
  many
• 1:01
  different
• 1:01
  ways
• 1:01
  we
• 1:01
  can
• 1:02
  elicit
• 1:02
  a
• 1:03
  cellular
• 1:03
  response
• 1:04
  or
• 1:04
  some
• 1:05
  kind
• 1:05
  of
• 1:05
  clinical
• 1:06
  effect.
• 1:06
  Some
• 1:07
  medications
• 1:08
  do
• 1:08
  it
• 1:08
  through
• 1:08
  intrinsic
• 1:09
  activity.
• 1:10
  In
• 1:10
  other
• 1:10
  words,
• 1:11
  they
• 1:11
  bind
• 1:11
  to
• 1:11
  a
• 1:12
  receptor
• 1:13
  and
• 1:13
  exert
• 1:14
  an
• 1:14
  effect,
• 1:15
  whether
• 1:15
  they
• 1:15
  be
• 1:15
  full
• 1:16
  agonists
• 1:16
  and
• 1:17
  exert
• 1:17
  a
• 1:17
  maximal
• 1:18
  effect
• 1:18
  on
• 1:19
  that
• 1:20
  receptor,
• 1:20
  whether
• 1:20
  they're
• 1:21
  a
• 1:21
  partial
• 1:21
  agonist.
• 1:22
  And
• 1:22
  they.
• 1:23
  They
• 1:23
  exert
• 1:23
  a
• 1:23
  partial
• 1:24
  effect,
• 1:24
  whether
• 1:25
  they're
• 1:25
  an
• 1:25
  antagonist
• 1:26
  where
• 1:27
  they
• 1:28
  actually
• 1:28
  don't
• 1:28
  activate
• 1:29
  it
• 1:29
  at
• 1:29
  all,
• 1:29
  or
• 1:29
  an
• 1:30
  inverse
• 1:30
  agonist.
• 1:31
  And
• 1:31
  we're
• 1:31
  gonna
• 1:31
  explain
• 1:31
  what
• 1:31
  that
• 1:32
  is,
• 1:32
  too.
• 1:33
  So
• 1:33
  you
• 1:33
  prescribe
• 1:34
  medications,
• 1:34
  they
• 1:35
  have
• 1:35
  intrinsic
• 1:36
  activity
• 1:37
  properties
• 1:37
  or
• 1:38
  act
• 1:38
  on
• 1:39
  targets
• 1:40
  in
• 1:41
  fundamentally
• 1:41
  different
• 1:42
  ways.
• 1:42
  Remember,
• 1:43
  not
• 1:43
  all
• 1:43
  of
• 1:43
  these
• 1:44
  medications
• 1:45
  are
• 1:46
  exerting
• 1:47
  their
• 1:47
  effects
• 1:48
  through
• 1:48
  this
• 1:48
  intrinsic
• 1:49
  activity.
• 1:49
  You
• 1:49
  have
• 1:49
  medications
• 1:50
  like
• 1:50
  SSRIs
• 1:51
  that
• 1:52
  involve
• 1:53
  transporters.
• 1:54
  You
• 1:55
  have
• 1:55
  other
• 1:55
  medications
• 1:56
  that
• 1:56
  influence
• 1:56
  intracellular
• 1:57
  signaling
• 1:58
  cascades
• 1:59
  like
• 2:00
  lithium.
• 2:01
  You
• 2:01
  have
• 2:02
  enzyme
• 2:03
  modulators,
• 2:03
  maois.
• 2:05
  You
• 2:05
  have
• 2:06
  calcium
• 2:06
  and
• 2:07
  sodium
• 2:07
  channel
• 2:08
  modulators
• 2:08
  like
• 2:09
  Gabapentin,
• 2:10
  Lamictal
• 2:11
  and
• 2:11
  Depakote.
• 2:12
  Medications
• 2:13
  can
• 2:13
  do
• 2:14
  different
• 2:14
  things
• 2:14
  in
• 2:14
  unique
• 2:15
  ways
• 2:15
  and
• 2:15
  target
• 2:16
  specific
• 2:16
  receptors
• 2:17
  at
• 2:17
  different
• 2:18
  affinities.
• 2:19
  Very
• 2:19
  important
• 2:19
  to
• 2:20
  understand
• 2:20
  that
• 2:20
  among
• 2:21
  so
• 2:21
  many
• 2:21
  other
• 2:21
  properties
• 2:22
  that
• 2:22
  influence
• 2:22
  how
• 2:23
  many
• 2:23
  receptors
• 2:24
  they
• 2:24
  actually
• 2:24
  occupy
• 2:25
  and
• 2:25
  why.
• 2:26
  And
• 2:26
  it's
• 2:27
  so
• 2:27
  exciting,
• 2:27
  and
• 2:27
  that's
• 2:28
  what
• 2:28
  makes
• 2:28
  this
• 2:28
  field
• 2:28
  so
• 2:29
  fun.
• 2:29
  But
• 2:29
  today
• 2:30
  we're
• 2:30
  going
• 2:30
  to
• 2:30
  talk
• 2:30
  about
• 2:31
  intrinsic
• 2:32
  activity.
• 2:33
  Now,
• 2:34
  you've
• 2:34
  probably
• 2:34
  seen
• 2:35
  this
• 2:35
  in
• 2:35
  your
• 2:35
  textbooks,
• 2:36
  right?
• 2:36
  And
• 2:36
  we're
• 2:37
  going
• 2:37
  to
• 2:37
  use
• 2:37
  a
• 2:37
  few
• 2:37
  analogies
• 2:38
  today
• 2:38
  to
• 2:38
  streamline
• 2:39
  this
• 2:39
  and
• 2:39
  make
• 2:39
  it
• 2:40
  make
• 2:40
  more
• 2:40
  sense
• 2:41
  to
• 2:41
  you.
• 2:41
  But
• 2:41
  let's
• 2:42
  start
• 2:42
  with
• 2:42
  full
• 2:42
  agonists.
• 2:43
  Now,
• 2:43
  what
• 2:44
  are
• 2:44
  full
• 2:44
  agonists?
• 2:44
  Full
• 2:45
  agonists
• 2:45
  bind
• 2:46
  to
• 2:46
  a
• 2:46
  receptor
• 2:47
  to
• 2:47
  produce
• 2:47
  the
• 2:47
  maximum
• 2:48
  possible
• 2:49
  biological
• 2:49
  response.
• 2:50
  They
• 2:51
  turn
• 2:51
  the
• 2:51
  heat
• 2:51
  up
• 2:52
  fully.
• 2:53
  The
• 2:53
  receptor
• 2:53
  fires
• 2:54
  at
• 2:54
  100%
• 2:54
  activity,
• 2:55
  okay?
• 2:56
  And
• 2:56
  this
• 2:57
  is
• 2:57
  almost
• 2:57
  like
• 2:58
  it's
• 2:58
  winter
• 2:58
  in
• 2:58
  your
• 2:59
  house
• 2:59
  and
• 2:59
  you're
• 2:59
  Cranking
• 3:00
  the
• 3:00
  heat
• 3:00
  up
• 3:00
  all
• 3:01
  the
• 3:01
  way
• 3:01
  that
• 3:02
  it
• 3:02
  can
• 3:02
  go.
• 3:02
  That's
• 3:03
  a
• 3:03
  full
• 3:03
  agonist,
• 3:04
  right?
• 3:04
  That's
• 3:05
  like
• 3:05
  morphine.
• 3:06
  That's
• 3:06
  like
• 3:06
  nicotine.
• 3:07
  It's
• 3:07
  a
• 3:07
  full
• 3:07
  agonist.
• 3:08
  You're
• 3:08
  getting
• 3:08
  maximal
• 3:09
  effect.
• 3:10
  Now,
• 3:10
  a
• 3:11
  partial
• 3:11
  agonist.
• 3:12
  If
• 3:12
  we're
• 3:12
  talking
• 3:12
  about
• 3:12
  thermostat
• 3:13
  analogies,
• 3:14
  which
• 3:14
  I
• 3:14
  usually
• 3:15
  hate,
• 3:15
  but
• 3:15
  in
• 3:15
  this
• 3:15
  case,
• 3:16
  I
• 3:16
  think
• 3:16
  it's
• 3:16
  very
• 3:16
  apt
• 3:17
  for
• 3:17
  what
• 3:17
  we're
• 3:17
  talking
• 3:18
  about.
• 3:18
  A
• 3:19
  partial
• 3:19
  agonist
• 3:20
  is
• 3:21
  always
• 3:21
  going
• 3:21
  to
• 3:21
  keep
• 3:21
  your
• 3:22
  temperature
• 3:22
  within
• 3:22
  a
• 3:23
  range
• 3:23
  of
• 3:23
  like,
• 3:23
  65
• 3:24
  to
• 3:24
  75
• 3:25
  degrees.
• 3:25
  It's
• 3:25
  going
• 3:25
  to
• 3:25
  keep
• 3:25
  it
• 3:26
  comfortable.
• 3:26
  Never
• 3:27
  too
• 3:27
  hot,
• 3:27
  never
• 3:28
  too
• 3:28
  cold,
• 3:29
  and
• 3:29
  so
• 3:30
  it
• 3:30
  stops
• 3:31
  the
• 3:31
  worst
• 3:31
  from
• 3:32
  happening.
• 3:32
  In
• 3:32
  this
• 3:32
  case,
• 3:33
  your
• 3:33
  home
• 3:33
  would
• 3:33
  just
• 3:34
  be
• 3:34
  overheating.
• 3:34
  You
• 3:34
  blow
• 3:35
  the
• 3:35
  furnace
• 3:35
  out.
• 3:36
  Right?
• 3:36
  That
• 3:36
  would
• 3:36
  be
• 3:36
  the
• 3:36
  equivalent
• 3:37
  of
• 3:37
  an
• 3:37
  overdose,
• 3:38
  fully
• 3:38
  agonizing
• 3:39
  these
• 3:39
  receptors
• 3:39
  where
• 3:40
  it
• 3:40
  depresses
• 3:40
  your
• 3:40
  respiratory
• 3:41
  drive.
• 3:42
  So
• 3:42
  a
• 3:42
  partial
• 3:42
  agonist
• 3:43
  puts
• 3:43
  a
• 3:44
  ceiling
• 3:44
  on
• 3:44
  that.
• 3:44
  Right?
• 3:45
  It's
• 3:45
  never
• 3:45
  too
• 3:45
  hot,
• 3:45
  never
• 3:46
  too
• 3:46
  cold.
• 3:46
  Your
• 3:47
  home
• 3:47
  is
• 3:47
  always
• 3:47
  going
• 3:47
  to
• 3:48
  be
• 3:48
  around
• 3:48
  65
• 3:48
  to
• 3:49
  75
• 3:49
  degrees.
• 3:50
  You're
• 3:50
  not
• 3:50
  going
• 3:50
  to
• 3:50
  be
• 3:51
  freezing
• 3:51
  to
• 3:51
  death
• 3:51
  in
• 3:51
  the
• 3:52
  winter,
• 3:52
  but
• 3:52
  you're
• 3:52
  not
• 3:53
  going
• 3:53
  to
• 3:53
  have
• 3:53
  the
• 3:53
  heat
• 3:53
  get
• 3:54
  cranked
• 3:54
  up
• 3:54
  so
• 3:54
  high
• 3:55
  that
• 3:55
  your
• 3:56
  furnace
• 3:56
  explodes
• 3:57
  and
• 3:57
  your
• 3:57
  house
• 3:57
  catches
• 3:58
  on
• 3:58
  fire.
• 3:58
  So
• 3:58
  it's
• 3:59
  a
• 3:59
  happy
• 3:59
  medium,
• 4:00
  a
• 4:00
  partial
• 4:00
  agonist.
• 4:01
  And
• 4:01
  we
• 4:01
  talk
• 4:01
  about
• 4:01
  partial
• 4:02
  agonists.
• 4:03
  We're
• 4:03
  talking
• 4:03
  about
• 4:03
  Rick,
• 4:04
  Salty,
• 4:04
  Abilify,
• 4:05
  Vraylar,
• 4:05
  Buspirone.
• 4:06
  Right?
• 4:06
  They
• 4:07
  have
• 4:07
  partial
• 4:07
  agonist
• 4:08
  effects
• 4:09
  where
• 4:10
  they
• 4:10
  act
• 4:11
  as
• 4:11
  buffers
• 4:12
  to
• 4:12
  extreme
• 4:12
  conditions.
• 4:13
  We've
• 4:14
  talked
• 4:14
  about
• 4:14
  Abilify
• 4:15
  in
• 4:15
  episodes
• 4:15
  previously.
• 4:16
  I
• 4:16
  highly
• 4:16
  encourage
• 4:17
  you
• 4:17
  to
• 4:17
  sift
• 4:18
  through
• 4:18
  our
• 4:18
  catalog.
• 4:19
  If
• 4:19
  you
• 4:19
  become
• 4:20
  a
• 4:20
  Patreon
• 4:20
  member,
• 4:20
  you'll
• 4:21
  have
• 4:21
  even
• 4:22
  more
• 4:22
  of
• 4:22
  a
• 4:22
  catalog.
• 4:23
  Go
• 4:23
  in
• 4:23
  our
• 4:24
  show
• 4:24
  notes
• 4:24
  and
• 4:24
  check
• 4:24
  that
• 4:25
  out
• 4:25
  and
• 4:25
  become
• 4:25
  a
• 4:25
  member.
• 4:25
  That
• 4:26
  would
• 4:26
  be
• 4:26
  great.
• 4:27
  The
• 4:28
  Abilify
• 4:29
  is
• 4:29
  buffering
• 4:30
  extremes,
• 4:31
  right?
• 4:31
  It's
• 4:31
  a
• 4:31
  D2
• 4:32
  partial
• 4:32
  agonist,
• 4:33
  so
• 4:33
  it
• 4:33
  stabilizes
• 4:34
  dopamine
• 4:34
  levels.
• 4:35
  It
• 4:35
  stabilizes
• 4:36
  dopamine
• 4:36
  tone
• 4:37
  in
• 4:37
  mesolimbic
• 4:38
  areas.
• 4:38
  So
• 4:39
  if
• 4:39
  there's
• 4:39
  excess
• 4:40
  dopaminergic
• 4:41
  tone
• 4:41
  in
• 4:41
  the
• 4:41
  mesolimbic
• 4:42
  areas
• 4:42
  of
• 4:42
  the
• 4:42
  brain,
• 4:43
  it
• 4:43
  will
• 4:43
  stabilize
• 4:44
  that.
• 4:44
  It
• 4:44
  will
• 4:44
  lower
• 4:45
  that
• 4:46
  baseline
• 4:47
  dopaminergic
• 4:48
  tone
• 4:48
  to
• 4:48
  mitigate
• 4:49
  psychosis
• 4:50
  or
• 4:50
  mood
• 4:50
  instability.
• 4:50
  It'll
• 4:51
  increase
• 4:51
  it
• 4:51
  in
• 4:52
  mesocortical
• 4:52
  areas,
• 4:53
  improving
• 4:54
  motivation
• 4:54
  and
• 4:54
  cognition.
• 4:56
  Right.
• 4:56
  And
• 4:56
  it'll
• 4:57
  also
• 4:57
  modulate
• 4:57
  the
• 4:58
  motor
• 4:58
  response
• 4:58
  so
• 4:59
  your
• 4:59
  EPS
• 5:00
  symptoms
• 5:00
  aren't
• 5:00
  as
• 5:00
  severe.
• 5:01
  Notice
• 5:01
  how
• 5:02
  it's
• 5:02
  playing
• 5:02
  like
• 5:03
  a
• 5:03
  thermostat
• 5:04
  where
• 5:04
  it's
• 5:04
  not
• 5:04
  too
• 5:04
  high?
• 5:05
  In
• 5:05
  this
• 5:05
  case,
• 5:05
  that
• 5:05
  would
• 5:06
  be
• 5:06
  dopaminergic
• 5:07
  circuits
• 5:07
  that
• 5:07
  are
• 5:07
  way
• 5:08
  too
• 5:08
  activated
• 5:09
  in
• 5:09
  mesolimbic
• 5:10
  areas,
• 5:10
  causing
• 5:11
  mania
• 5:11
  or
• 5:11
  Psychosis.
• 5:12
  So
• 5:12
  it's
• 5:13
  stabilizing
• 5:13
  that
• 5:13
  the
• 5:14
  home
• 5:14
  is
• 5:14
  not
• 5:14
  getting
• 5:15
  blasted
• 5:15
  with
• 5:15
  heat
• 5:15
  to
• 5:16
  the
• 5:16
  point
• 5:16
  where
• 5:16
  the
• 5:16
  furnace
• 5:17
  is
• 5:17
  exploding.
• 5:17
  It's
• 5:18
  dialing
• 5:18
  that
• 5:18
  down.
• 5:19
  Right.
• 5:19
  So
• 5:19
  in
• 5:19
  areas
• 5:20
  where
• 5:20
  the
• 5:20
  dopamine
• 5:21
  is
• 5:21
  too
• 5:21
  high
• 5:22
  and
• 5:22
  the
• 5:22
  partial
• 5:22
  agonist
• 5:23
  will
• 5:23
  actually
• 5:24
  cool
• 5:25
  it
• 5:25
  down
• 5:25
  and
• 5:26
  keep
• 5:26
  it
• 5:26
  kind
• 5:26
  of
• 5:27
  always
• 5:27
  in
• 5:27
  the
• 5:27
  middle,
• 5:27
  again,
• 5:28
  always.
• 5:28
  65
• 5:28
  to
• 5:29
  75,
• 5:30
  always.
• 5:30
  And
• 5:30
  that's
• 5:31
  just
• 5:31
  a
• 5:31
  temperature
• 5:32
  analogy,
• 5:32
  right?
• 5:33
  It
• 5:33
  keeps
• 5:33
  the
• 5:33
  temperature
• 5:34
  at
• 5:34
  65,
• 5:34
  75.
• 5:35
  What
• 5:35
  it
• 5:36
  actually
• 5:36
  does
• 5:36
  in
• 5:37
  these
• 5:37
  specific
• 5:37
  circuits
• 5:38
  might
• 5:38
  vary
• 5:38
  in
• 5:38
  terms
• 5:39
  of
• 5:39
  percentage
• 5:40
  occupancy
• 5:41
  or
• 5:41
  the
• 5:41
  actual
• 5:41
  percentage,
• 5:42
  the
• 5:43
  tone
• 5:43
  by
• 5:43
  which
• 5:43
  it
• 5:43
  exerts
• 5:44
  the
• 5:44
  effect.
• 5:45
  But
• 5:45
  the
• 5:45
  big
• 5:45
  takeaway
• 5:46
  is
• 5:46
  abilifying
• 5:47
  lightly
• 5:48
  pushes
• 5:48
  on
• 5:48
  the
• 5:48
  gas
• 5:49
  so
• 5:49
  that
• 5:50
  those
• 5:50
  circuits
• 5:51
  are
• 5:51
  not
• 5:51
  being
• 5:51
  overwhelmed
• 5:52
  with
• 5:53
  dopamine,
• 5:53
  but
• 5:54
  still
• 5:54
  have
• 5:54
  some
• 5:55
  dopaminergic
• 5:56
  activity
• 5:57
  associated
• 5:57
  with
• 5:57
  them.
• 5:57
  Remember,
• 5:58
  if
• 5:58
  you
• 5:58
  have
• 5:58
  Haldol,
• 5:59
  which
• 5:59
  would
• 6:00
  be
• 6:00
  like
• 6:00
  your
• 6:01
  classic
• 6:01
  antagonist,
• 6:02
  you're
• 6:03
  blocking
• 6:03
  the
• 6:03
  receptor,
• 6:04
  right?
• 6:04
  And
• 6:05
  with
• 6:05
  antagonists,
• 6:06
  you
• 6:06
  bind
• 6:06
  to
• 6:06
  the
• 6:07
  receptor
• 6:07
  and
• 6:07
  you
• 6:07
  don't
• 6:08
  activate
• 6:08
  it.
• 6:09
  So
• 6:09
  the
• 6:09
  equivalent
• 6:09
  here
• 6:10
  would
• 6:10
  be
• 6:10
  locking
• 6:10
  the
• 6:11
  thermostat
• 6:11
  at
• 6:12
  70.
• 6:12
  Nobody
• 6:13
  can
• 6:13
  change
• 6:13
  it.
• 6:14
  And,
• 6:14
  well,
• 6:14
  that
• 6:14
  can
• 6:14
  make
• 6:15
  a
• 6:15
  lot
• 6:15
  of
• 6:15
  people
• 6:15
  very
• 6:15
  uncomfortable.
• 6:16
  Just
• 6:16
  like
• 6:16
  with
• 6:17
  Haldol,
• 6:18
  it
• 6:19
  locks
• 6:19
  it
• 6:20
  at
• 6:20
  70,
• 6:20
  so
• 6:21
  it
• 6:21
  blocks
• 6:21
  the
• 6:21
  dopamine
• 6:22
  receptors.
• 6:22
  And
• 6:22
  there
• 6:22
  are
• 6:23
  some
• 6:24
  motor
• 6:25
  side
• 6:25
  effects
• 6:25
  that
• 6:25
  are
• 6:25
  very
• 6:25
  unpleasant.
• 6:26
  With
• 6:26
  Haldol,
• 6:27
  however,
• 6:27
  it's
• 6:28
  also
• 6:28
  locking
• 6:29
  the
• 6:29
  thermostat
• 6:29
  at
• 6:30
  70.
• 6:30
  Right.
• 6:30
  So
• 6:30
  it's
• 6:31
  kind
• 6:31
  of
• 6:31
  protecting
• 6:31
  you
• 6:31
  a
• 6:32
  little
• 6:32
  bit,
• 6:32
  too,
• 6:33
  in
• 6:33
  terms
• 6:33
  of
• 6:33
  a
• 6:33
  dopamine
• 6:34
  blockade.
• 6:34
  It
• 6:34
  will
• 6:35
  mitigate
• 6:35
  psychosis,
• 6:36
  so
• 6:36
  it'll
• 6:36
  prevent
• 6:36
  that
• 6:36
  furnace
• 6:37
  from
• 6:37
  blowing
• 6:37
  out
• 6:38
  and
• 6:38
  getting
• 6:38
  way
• 6:38
  too
• 6:38
  hot.
• 6:39
  But
• 6:40
  it's
• 6:40
  also
• 6:41
  going
• 6:41
  to
• 6:41
  kind
• 6:41
  of
• 6:42
  lock
• 6:42
  you
• 6:42
  at
• 6:43
  70.
• 6:43
  And
• 6:44
  even
• 6:44
  70
• 6:44
  can
• 6:44
  be
• 6:44
  a
• 6:45
  little
• 6:45
  too
• 6:45
  hot
• 6:45
  for
• 6:45
  some
• 6:46
  people.
• 6:46
  Right.
• 6:46
  It
• 6:46
  doesn't
• 6:46
  have
• 6:46
  that
• 6:47
  flexibility
• 6:48
  of
• 6:48
  Abilify
• 6:49
  that
• 6:49
  keeps
• 6:50
  things
• 6:50
  in
• 6:50
  the
• 6:50
  middle.
• 6:51
  It's
• 6:52
  an
• 6:52
  antagonist.
• 6:53
  It
• 6:53
  just
• 6:53
  means
• 6:53
  that
• 6:54
  it
• 6:54
  doesn't
• 6:54
  really
• 6:54
  raise
• 6:55
  or
• 6:55
  lower
• 6:55
  the
• 6:55
  temperature
• 6:56
  itself.
• 6:56
  It
• 6:56
  just
• 6:56
  blocks
• 6:57
  anybody
• 6:57
  else
• 6:58
  from
• 6:58
  adjusting
• 6:58
  the
• 6:58
  thermostat
• 6:59
  at
• 7:00
  that
• 7:00
  time.
• 7:00
  If
• 7:01
  this
• 7:01
  was
• 7:01
  a
• 7:01
  nightclub,
• 7:02
  analogy
• 7:03
  would
• 7:03
  be
• 7:03
  the
• 7:04
  bouncer
• 7:04
  that
• 7:04
  says
• 7:04
  nobody
• 7:05
  else
• 7:05
  is
• 7:05
  going
• 7:05
  to
• 7:05
  the
• 7:06
  dance
• 7:06
  floor.
• 7:06
  The
• 7:06
  full
• 7:07
  agonist
• 7:07
  would
• 7:07
  be
• 7:08
  the
• 7:08
  guy
• 7:08
  in
• 7:08
  the
• 7:08
  middle
• 7:08
  of
• 7:09
  the
• 7:09
  dance
• 7:09
  floor,
• 7:09
  break
• 7:10
  dancing,
• 7:10
  drinking
• 7:11
  too
• 7:11
  much,
• 7:11
  partying
• 7:12
  wild.
• 7:13
  The
• 7:13
  music's
• 7:13
  going
• 7:14
  crazy.
• 7:14
  He's
• 7:14
  the
• 7:14
  full
• 7:15
  agonist.
• 7:15
  The
• 7:15
  antagonist
• 7:16
  is
• 7:16
  the
• 7:16
  bouncer
• 7:16
  saying,
• 7:17
  nobody
• 7:17
  left.
• 7:18
  Nobody
• 7:18
  else
• 7:19
  is
• 7:19
  coming
• 7:19
  into
• 7:19
  the
• 7:20
  club.
• 7:20
  The
• 7:20
  partial
• 7:21
  agonist
• 7:21
  would
• 7:21
  be
• 7:22
  like
• 7:22
  a
• 7:22
  guy
• 7:22
  who's
• 7:22
  not
• 7:22
  breakdancing,
• 7:23
  but
• 7:24
  he's
• 7:24
  in
• 7:24
  the
• 7:24
  middle
• 7:24
  of
• 7:24
  the
• 7:24
  dance
• 7:25
  floor,
• 7:25
  just
• 7:25
  kind
• 7:25
  of
• 7:25
  gently
• 7:26
  swaying
• 7:26
  his
• 7:26
  hips
• 7:27
  like
• 7:27
  a
• 7:27
  total
• 7:28
  nerd.
• 7:28
  Maybe
• 7:28
  he's
• 7:28
  Only
• 7:29
  drinking
• 7:29
  one
• 7:29
  glass
• 7:30
  of
• 7:30
  wine.
• 7:30
  He's
• 7:31
  not
• 7:31
  partying
• 7:31
  really
• 7:32
  hard.
• 7:33
  He's
• 7:33
  not
• 7:33
  doing
• 7:33
  anything
• 7:33
  illegal.
• 8:29
  He's
• 8:29
  not
• 8:29
  dancing
• 8:30
  like
• 8:30
  a
• 7:35
  maniac.
• 8:31
  He's
• 8:31
  just
• 8:31
  kind
• 8:31
  of
• 8:31
  swaying
• 8:32
  his
• 8:32
  hips
• 8:32
  in
• 8:32
  a
• 8:33
  nerdy
• 8:33
  way
• 8:34
  and
• 8:34
  pointing
• 8:35
  his
• 8:35
  index
• 8:35
  finger
• 8:36
  in
• 8:36
  the
• 8:36
  air,
• 8:37
  being
• 8:37
  kind
• 8:37
  of
• 8:37
  nerdy
• 8:38
  and
• 8:38
  chill.
• 8:39
  And
• 8:39
  that's
• 8:39
  a
• 8:39
  partial
• 8:40
  agonist,
• 8:40
  right?
• 8:40
  The
• 8:41
  party's
• 8:41
  kind
• 8:41
  of
• 8:41
  moving,
• 8:41
  it's
• 8:42
  swaying,
• 8:42
  kind
• 8:42
  of
• 8:42
  low
• 8:43
  grade.
• 8:43
  It's
• 8:43
  not
• 8:43
  boring
• 8:44
  where
• 8:44
  it's.
• 8:45
  The
• 8:45
  music's
• 8:45
  off
• 8:46
  and
• 8:46
  everybody's
• 8:47
  drinking
• 8:47
  water,
• 8:48
  but
• 8:48
  it's
• 8:49
  just
• 8:49
  kind
• 8:49
  of
• 8:49
  flowing
• 8:49
  a
• 8:50
  little
• 8:50
  bit.
• 8:50
  But
• 8:50
  it's
• 8:50
  certainly
• 8:51
  not
• 8:51
  flowing
• 8:51
  to
• 8:51
  the
• 8:52
  point
• 8:52
  where
• 8:53
  this
• 8:53
  guy's
• 8:54
  breakdancing
• 8:54
  in
• 8:54
  the
• 8:54
  middle
• 8:55
  of
• 8:55
  the
• 8:55
  floor,
• 8:55
  going
• 8:56
  berserko,
• 8:57
  right?
• 8:57
  And
• 8:57
  then
• 8:57
  Haldol,
• 8:58
  again,
• 8:58
  is
• 8:58
  the
• 8:58
  bouncer
• 8:59
  who's
• 8:59
  like,
• 8:59
  no
• 9:00
  more
• 9:00
  people
• 9:00
  come
• 9:00
  in
• 9:01
  here.
• 9:01
  This
• 9:01
  party's
• 9:02
  not
• 9:02
  getting
• 9:02
  any
• 9:02
  more
• 9:03
  intense.
• 9:03
  The
• 9:04
  doors
• 9:04
  are
• 9:04
  locked,
• 9:05
  and
• 9:05
  so
• 9:05
  nobody
• 9:05
  can
• 9:06
  come
• 9:06
  in
• 9:06
  and
• 9:06
  further
• 9:06
  stimulate
• 9:07
  the
• 9:07
  dance
• 9:07
  floor
• 9:08
  or
• 9:08
  do
• 9:08
  anything.
• 9:08
  And
• 9:08
  again,
• 9:09
  Haldol
• 9:10
  would
• 9:10
  be
• 9:10
  a
• 9:10
  very
• 9:10
  good
• 9:11
  example
• 9:11
  of
• 9:12
  an
• 9:12
  antagonist.
• 9:12
  So
• 9:12
  would
• 9:13
  naltrexone.
• 9:13
  Right?
• 9:13
  Naltrexone
• 9:14
  blocks
• 9:14
  the
• 9:14
  opioid
• 9:15
  receptors.
• 9:16
  Risperdal,
• 9:17
  Zyprexa,
• 9:17
  those
• 9:17
  are
• 9:18
  also
• 9:18
  antagonists.
• 9:19
  In
• 9:19
  other
• 9:19
  words,
• 9:20
  they
• 9:20
  stop
• 9:20
  other
• 9:21
  signals,
• 9:21
  but
• 9:22
  they
• 9:22
  don't
• 9:22
  really
• 9:22
  change
• 9:23
  baseline
• 9:23
  signaling
• 9:24
  necessarily.
• 9:25
  They're
• 9:25
  antagonists.
• 9:26
  They
• 9:26
  stop
• 9:27
  more
• 9:27
  of
• 9:27
  these
• 9:28
  breakdancers
• 9:28
  from
• 9:28
  coming
• 9:29
  in
• 9:29
  and
• 9:29
  lighting
• 9:29
  up
• 9:30
  the
• 9:30
  floor
• 9:30
  like
• 9:30
  a
• 9:30
  full
• 9:31
  agonist
• 9:31
  would.
• 9:32
  If
• 9:32
  you're
• 9:32
  a
• 9:32
  bouncer
• 9:33
  or
• 9:33
  you're
• 9:33
  the
• 9:34
  host
• 9:34
  of
• 9:34
  this
• 9:34
  party,
• 9:35
  you
• 9:35
  don't
• 9:35
  want
• 9:35
  it
• 9:35
  to
• 9:35
  get
• 9:35
  too
• 9:36
  crazy.
• 9:36
  A
• 9:36
  partial
• 9:36
  agonist
• 9:37
  is
• 9:37
  kind
• 9:37
  of
• 9:37
  the
• 9:37
  best
• 9:38
  thing,
• 9:38
  right?
• 9:38
  It's
• 9:38
  never
• 9:38
  dull,
• 9:39
  but
• 9:39
  it's
• 9:40
  never
• 9:40
  someone
• 9:41
  breakdancing
• 9:42
  with
• 9:42
  glow
• 9:42
  sticks,
• 9:42
  drinking
• 9:43
  too
• 9:43
  much
• 9:43
  and
• 9:43
  starting
• 9:44
  fights.
• 9:44
  A
• 9:44
  full
• 9:44
  agonist
• 9:45
  can
• 9:45
  be
• 9:45
  pretty
• 9:46
  extreme.
• 9:46
  You
• 9:47
  want
• 9:47
  something
• 9:47
  right
• 9:47
  in
• 9:47
  the
• 9:47
  middle.
• 9:48
  And
• 9:48
  that's
• 9:48
  why
• 9:48
  Abilify
• 9:49
  has
• 9:49
  so
• 9:50
  many
• 9:50
  broad
• 9:51
  clinical
• 9:51
  applications.
• 9:52
  It
• 9:52
  can
• 9:52
  help
• 9:53
  with.
• 9:53
  As
• 9:53
  an
• 9:53
  adjunct
• 9:54
  to
• 9:54
  depression,
• 9:55
  where
• 9:55
  you're
• 9:56
  not
• 9:56
  shut
• 9:56
  down
• 9:56
  all
• 9:56
  the
• 9:57
  way,
• 9:57
  it's
• 9:57
  kind
• 9:57
  of
• 9:57
  activating
• 9:58
  some
• 9:58
  of
• 9:58
  those
• 9:59
  dopaminergic
• 10:00
  areas
• 10:01
  that
• 10:01
  are
• 10:01
  understimulated.
• 10:02
  But
• 10:02
  again,
• 10:02
  it's
• 10:02
  putting
• 10:03
  a
• 10:03
  ceiling.
• 10:03
  It's
• 10:04
  calming
• 10:04
  things
• 10:04
  down.
• 10:05
  It's
• 10:05
  not
• 10:05
  letting
• 10:05
  that
• 10:06
  thermostat
• 10:06
  go
• 10:07
  all
• 10:07
  the
• 10:07
  way
• 10:07
  to
• 10:07
  90.
• 10:08
  It's
• 10:08
  just
• 10:08
  kind
• 10:08
  of
• 10:09
  chill.
• 10:09
  So
• 10:09
  again,
• 10:10
  that's
• 10:10
  partial
• 10:10
  agonism.
• 10:11
  Another
• 10:11
  way
• 10:12
  to
• 10:12
  look
• 10:12
  at
• 10:12
  this
• 10:12
  is
• 10:12
  like
• 10:13
  a
• 10:13
  light
• 10:13
  switch,
• 10:13
  right?
• 10:13
  You're
• 10:14
  turning
• 10:14
  on
• 10:14
  the
• 10:15
  lights,
• 10:15
  full
• 10:15
  capacity,
• 10:16
  fully
• 10:16
  bright.
• 10:17
  That's
• 10:17
  a
• 10:17
  full
• 10:17
  agonist.
• 10:18
  Partial
• 10:18
  agonist
• 10:19
  is
• 10:19
  like
• 10:19
  a
• 10:19
  dimmer
• 10:19
  switch.
• 10:20
  The
• 10:20
  light
• 10:20
  is
• 10:21
  just
• 10:21
  on
• 10:21
  a
• 10:21
  little
• 10:21
  bit.
• 10:21
  It's
• 10:22
  kind
• 10:22
  of
• 10:22
  a
• 10:22
  nice
• 10:22
  Glow,
• 10:23
  not
• 10:23
  too
• 10:23
  bright,
• 10:24
  not
• 10:25
  dark.
• 10:25
  It's
• 10:26
  just
• 10:26
  a
• 10:26
  little
• 10:26
  bit
• 10:27
  cozy.
• 10:28
  The
• 10:28
  antagonist
• 10:29
  would
• 10:29
  be
• 10:29
  like,
• 10:29
  you
• 10:29
  can't
• 10:29
  turn
• 10:30
  the
• 10:30
  light
• 10:30
  on
• 10:31
  or
• 10:31
  off.
• 10:31
  It's
• 10:32
  blocking
• 10:32
  any
• 10:32
  activity
• 10:33
  to
• 10:33
  modulate
• 10:33
  the
• 10:33
  light.
• 10:34
  An
• 10:34
  inverse
• 10:35
  agonist
• 10:35
  would
• 10:36
  be
• 10:36
  like
• 10:36
  turning
• 10:36
  the
• 10:36
  heat
• 10:37
  below
• 10:37
  the
• 10:38
  normal
• 10:38
  70
• 10:39
  degree
• 10:39
  heat,
• 10:40
  and
• 10:40
  now
• 10:40
  it's
• 10:40
  like
• 10:40
  60.
• 10:41
  In
• 10:41
  other
• 10:41
  words,
• 10:41
  these
• 10:42
  are
• 10:42
  drugs
• 10:42
  that
• 10:42
  bind
• 10:43
  to
• 10:43
  and
• 10:43
  reduce
• 10:44
  the
• 10:44
  receptors.
• 10:45
  Baseline
• 10:46
  activity
• 10:46
  below
• 10:46
  resting
• 10:47
  level.
• 10:47
  And
• 10:48
  for
• 10:48
  this
• 10:48
  particular
• 10:49
  analogy,
• 10:49
  I
• 10:49
  think
• 10:50
  a
• 10:50
  nightclub
• 10:50
  is
• 10:51
  a
• 10:51
  better
• 10:51
  way
• 10:51
  to
• 10:51
  look
• 10:51
  at
• 10:52
  this,
• 10:52
  right?
• 10:52
  The
• 10:52
  nightclub
• 10:53
  dance
• 10:53
  club
• 10:53
  I
• 10:53
  was
• 10:53
  talking
• 10:54
  about,
• 10:54
  where
• 10:55
  the
• 10:55
  bouncers
• 10:56
  say,
• 10:56
  nope,
• 10:57
  no
• 10:57
  one
• 10:57
  else
• 10:57
  comes
• 10:58
  in.
• 10:58
  That's
• 10:58
  the
• 10:58
  antagonist.
• 10:59
  The
• 10:59
  inverse
• 11:00
  agonist
• 11:00
  would
• 11:01
  be
• 11:01
  like,
• 11:01
  police
• 11:01
  that
• 11:02
  come
• 11:02
  in
• 11:02
  and
• 11:02
  throw
• 11:02
  people
• 11:03
  out.
• 11:03
  They're
• 11:03
  like,
• 11:03
  okay,
• 11:04
  you
• 11:04
  the
• 11:04
  slow
• 11:04
  dancer
• 11:05
  out.
• 11:05
  You,
• 11:05
  the
• 11:06
  fast
• 11:06
  dancer,
• 11:06
  out.
• 11:07
  You
• 11:07
  the
• 11:07
  guy
• 11:07
  taking
• 11:07
  shots
• 11:08
  of
• 11:08
  Jack
• 11:08
  Daniels,
• 11:09
  you're
• 11:09
  leaving
• 11:09
  too,
• 11:09
  right?
• 11:10
  Hey,
• 11:10
  you
• 11:10
  in
• 11:10
  the
• 11:10
  conga
• 11:11
  line,
• 11:11
  you're
• 11:11
  out.
• 11:12
  Those
• 11:12
  are
• 11:13
  medications
• 11:13
  that
• 11:14
  not
• 11:14
  only
• 11:15
  kind
• 11:15
  of
• 11:15
  lower
• 11:16
  the
• 11:16
  temperature,
• 11:17
  but
• 11:17
  they
• 11:17
  reduce
• 11:18
  the
• 11:18
  actual
• 11:19
  baseline
• 11:19
  activity
• 11:20
  of
• 11:20
  the
• 11:20
  party.
• 11:20
  Now,
• 11:20
  the
• 11:20
  party
• 11:21
  didn't
• 11:21
  just
• 11:22
  quiet
• 11:22
  down.
• 11:23
  It's
• 11:23
  not
• 11:23
  some
• 11:23
  dimmer
• 11:24
  switch.
• 11:24
  This
• 11:24
  is
• 11:25
  now
• 11:25
  reducing
• 11:26
  the
• 11:26
  actual
• 11:26
  baseline
• 11:27
  activity
• 11:27
  of
• 11:27
  the
• 11:27
  party.
• 11:28
  So
• 11:28
  the
• 11:29
  normal
• 11:29
  chatter,
• 11:29
  the
• 11:30
  normal
• 11:30
  dancing,
• 11:30
  the
• 11:31
  party
• 11:31
  is
• 11:32
  actually
• 11:32
  less
• 11:32
  lively
• 11:33
  and
• 11:33
  less
• 11:33
  engaged
• 11:34
  than
• 11:34
  it
• 11:34
  was
• 11:34
  before.
• 11:34
  That's
• 11:35
  an
• 11:35
  inverse
• 11:35
  agonist.
• 11:36
  The
• 11:36
  cops
• 11:36
  who
• 11:36
  say,
• 11:37
  all
• 11:37
  right,
• 11:37
  everybody
• 11:38
  go
• 11:38
  home.
• 11:38
  Time
• 11:38
  to
• 11:39
  leave.
• 11:39
  Last
• 11:40
  call,
• 11:41
  everybody
• 11:41
  out.
• 11:42
  And
• 11:42
  those
• 11:42
  medications
• 11:43
  would
• 11:43
  be
• 11:43
  like
• 11:43
  mirtazapine.
• 11:44
  It's
• 11:44
  an
• 11:44
  H1
• 11:45
  inverse
• 11:45
  agonist,
• 11:46
  which
• 11:46
  actually
• 11:47
  not
• 11:48
  only
• 11:48
  makes
• 11:48
  you
• 11:49
  sleepy
• 11:49
  by
• 11:49
  antagonizing
• 11:50
  histamine,
• 11:51
  but
• 11:51
  it
• 11:51
  lowers
• 11:52
  the
• 11:53
  ordinary
• 11:53
  baseline
• 11:54
  histamine
• 11:55
  activity,
• 11:55
  making
• 11:56
  you
• 11:56
  more
• 11:56
  sedated
• 11:57
  than
• 11:57
  you
• 11:57
  normally
• 11:58
  would
• 11:58
  be.
• 11:58
  Histamine
• 11:59
  is
• 11:59
  a
• 11:59
  wakefulness
• 12:00
  neurotransmitter.
• 12:01
  It's
• 12:01
  all
• 12:01
  about
• 12:01
  your
• 12:02
  wakefulness
• 12:02
  circuits.
• 12:03
  Inverse
• 12:03
  agonists
• 12:04
  come
• 12:04
  in
• 12:04
  and
• 12:04
  actively
• 12:05
  suppress
• 12:05
  an
• 12:05
  overactive
• 12:06
  baseline,
• 12:07
  like
• 12:07
  with
• 12:07
  histamine,
• 12:08
  so
• 12:08
  you're
• 12:08
  more
• 12:08
  tired.
• 12:09
  It's
• 12:09
  kind
• 12:10
  of
• 12:10
  like
• 12:10
  a
• 12:10
  vacuum
• 12:10
  effect.
• 12:11
  You're
• 12:11
  vacuuming
• 12:11
  the
• 12:12
  baseline
• 12:12
  activity
• 12:13
  even
• 12:13
  lower.
• 12:13
  Notice
• 12:14
  how
• 12:14
  that's
• 12:14
  fundamentally
• 12:15
  different
• 12:15
  than
• 12:16
  just
• 12:16
  a
• 12:16
  bouncer
• 12:17
  who
• 12:17
  says,
• 12:17
  nobody
• 12:17
  else
• 12:17
  can
• 12:18
  come
• 12:18
  in
• 12:18
  here.
• 12:18
  We
• 12:19
  can't
• 12:19
  activate
• 12:19
  any
• 12:20
  of
• 12:20
  these
• 12:20
  receptors.
• 12:20
  No
• 12:21
  one
• 12:21
  else
• 12:21
  is
• 12:21
  having
• 12:22
  fun
• 12:22
  on
• 12:22
  the
• 12:22
  dance
• 12:22
  floor.
• 12:22
  The
• 12:23
  antagonist
• 12:23
  plays,
• 12:23
  blocks
• 12:24
  any
• 12:24
  more
• 12:24
  activity.
• 12:25
  The
• 12:25
  partial
• 12:25
  agonist
• 12:26
  is
• 12:26
  like
• 12:26
  a
• 12:26
  diplomat
• 12:27
  compromising
• 12:28
  between
• 12:29
  two
• 12:29
  extremes
• 12:29
  and
• 12:30
  a
• 12:30
  full
• 12:30
  agonist.
• 12:31
  Each
• 12:31
  of
• 12:31
  these
• 12:32
  has
• 12:32
  their
• 12:32
  place
• 12:32
  in
• 12:33
  psychopharmacology.
• 12:34
  This
• 12:35
  isn't
• 12:35
  necessarily
• 12:36
  a
• 12:36
  conversation
• 12:36
  between
• 12:37
  what's
• 12:38
  the
• 12:38
  best
• 12:38
  or
• 12:38
  what's
• 12:38
  the
• 12:38
  worst.
• 12:39
  These
• 12:39
  are
• 12:39
  just
• 12:39
  mechanisms
• 12:40
  by
• 12:40
  which
• 12:40
  drugs
• 12:41
  exert
• 12:42
  their
• 12:42
  effects.
• 12:42
  And
• 12:43
  notice,
• 12:43
  I
• 12:43
  used
• 12:44
  nicotine
• 12:44
  and
• 12:44
  morphine
• 12:45
  as
• 12:45
  examples,
• 12:45
  but
• 12:45
  nicotine,
• 12:46
  right
• 12:46
  this
• 12:47
  isn't
• 12:47
  even
• 12:47
  just
• 12:48
  medications
• 12:48
  we're
• 12:49
  talking
• 12:49
  about.
• 12:49
  Heroin
• 12:50
  is
• 12:50
  a
• 12:50
  full
• 12:50
  agonist,
• 12:51
  right?
• 12:51
  Full
• 12:51
  agonists
• 12:52
  in
• 12:52
  certain
• 12:53
  extremes
• 12:53
  can
• 12:54
  lead
• 12:54
  to
• 12:54
  a
• 12:54
  lethal
• 12:55
  overdose.
• 12:55
  They
• 12:56
  completely
• 12:56
  suppress
• 12:57
  the
• 12:57
  respiratory
• 12:58
  drive.
• 12:58
  You've
• 12:59
  probably
• 12:59
  heard
• 13:00
  about
• 13:00
  buprenorphine,
• 13:01
  which
• 13:01
  is
• 13:01
  a
• 13:01
  partial
• 13:01
  agonist.
• 13:02
  It's
• 13:02
  an
• 13:03
  opioid
• 13:03
  partial
• 13:04
  agonist
• 13:04
  on
• 13:04
  the
• 13:05
  mu
• 13:05
  receptor.
• 13:05
  It
• 13:06
  gives
• 13:06
  enough
• 13:06
  activation
• 13:07
  to
• 13:07
  prevent
• 13:08
  opioid
• 13:08
  withdrawal
• 13:09
  and
• 13:10
  cravings,
• 13:10
  but
• 13:11
  it
• 13:11
  blocks
• 13:11
  the
• 13:11
  full
• 13:11
  agonist,
• 13:12
  like
• 13:12
  heroin
• 13:13
  or
• 13:13
  fentanyl,
• 13:14
  from
• 13:14
  exerting
• 13:15
  their
• 13:15
  full
• 13:15
  effect
• 13:15
  to
• 13:15
  an
• 13:16
  overdose.
• 13:17
  It
• 13:17
  balances
• 13:17
  the
• 13:17
  system.
• 13:18
  It
• 13:18
  prevents
• 13:18
  extremes.
• 13:19
  And,
• 13:20
  you
• 13:20
  know,
• 13:20
  whether
• 13:20
  we're
• 13:21
  talking
• 13:21
  about
• 13:21
  preventing
• 13:22
  mania
• 13:23
  or
• 13:24
  withdrawal,
• 13:25
  you
• 13:25
  can
• 13:25
  see
• 13:25
  on
• 13:25
  both
• 13:26
  ends
• 13:26
  of
• 13:26
  the
• 13:26
  spectrum,
• 13:26
  that's
• 13:27
  really
• 13:27
  important.
• 13:27
  Just
• 13:28
  like
• 13:28
  our
• 13:28
  nightclub
• 13:28
  analogy,
• 13:29
  right?
• 13:29
  We
• 13:30
  want
• 13:30
  some
• 13:30
  guy
• 13:30
  kind
• 13:31
  of
• 13:31
  gently
• 13:31
  swaying
• 13:31
  his
• 13:31
  hips
• 13:32
  and
• 13:32
  chilling
• 13:32
  and
• 13:32
  having
• 13:33
  wine.
• 13:33
  We
• 13:33
  don't
• 13:33
  want
• 13:34
  the
• 13:34
  party
• 13:34
  to
• 13:34
  die.
• 13:35
  We
• 13:35
  don't
• 13:35
  want
• 13:35
  the
• 13:35
  party
• 13:35
  to
• 13:36
  be
• 13:36
  so
• 13:36
  boring
• 13:37
  and
• 13:37
  dull
• 13:37
  that
• 13:38
  everyone
• 13:38
  goes
• 13:38
  home.
• 13:38
  We
• 13:39
  want
• 13:39
  some
• 13:39
  activity.
• 13:40
  We
• 13:40
  just
• 13:40
  don't
• 13:40
  want
• 13:41
  this
• 13:41
  to
• 13:41
  be
• 13:41
  a
• 13:41
  rave
• 13:41
  where
• 13:41
  the
• 13:42
  cops
• 13:42
  get
• 13:42
  called.
• 13:42
  That.
• 13:43
  That
• 13:43
  would
• 13:43
  be
• 13:43
  the
• 13:43
  infer.
• 13:43
  Cops
• 13:44
  get
• 13:44
  called,
• 13:45
  and
• 13:45
  now
• 13:45
  everybody's
• 13:46
  thrown
• 13:46
  out.
• 13:46
  And
• 13:46
  the
• 13:47
  baseline
• 13:47
  tone
• 13:47
  of
• 13:48
  the
• 13:48
  party
• 13:48
  is
• 13:48
  radically
• 13:49
  lowered
• 13:50
  than
• 13:50
  before.
• 13:51
  Right?
• 13:51
  The
• 13:52
  antagonists
• 13:52
  can
• 13:52
  be
• 13:53
  a
• 13:53
  good
• 13:53
  thing,
• 13:53
  too,
• 13:53
  because
• 13:54
  we
• 13:54
  might
• 13:54
  have
• 13:54
  overactivity.
• 13:55
  The
• 13:55
  party
• 13:55
  might
• 13:56
  be
• 13:56
  way
• 13:56
  too
• 13:56
  crazy
• 13:57
  and
• 13:57
  loud,
• 13:58
  and
• 13:58
  the
• 13:58
  neighbors
• 13:59
  are
• 13:59
  getting
• 14:00
  really
• 14:01
  annoyed
• 14:01
  by
• 14:02
  the
• 14:02
  noise
• 14:02
  across
• 14:02
  the
• 14:03
  street
• 14:03
  in
• 14:03
  the
• 14:03
  nightclub.
• 14:04
  And
• 14:04
  the
• 14:04
  bouncers
• 14:05
  antagonizing
• 14:05
  the
• 14:05
  door,
• 14:06
  saying,
• 14:06
  hey,
• 14:06
  no
• 14:06
  one
• 14:07
  else
• 14:07
  is
• 14:07
  coming
• 14:07
  in.
• 14:07
  So
• 14:07
  that
• 14:08
  kind
• 14:08
  of
• 14:08
  helps
• 14:09
  reduce
• 14:09
  the
• 14:10
  level
• 14:10
  of
• 14:10
  excitement,
• 14:11
  which
• 14:11
  can
• 14:11
  be
• 14:12
  great,
• 14:12
  right?
• 14:12
  If
• 14:12
  you're
• 14:13
  antagonizing
• 14:13
  dopamine
• 14:14
  receptors
• 14:15
  when
• 14:15
  it
• 14:15
  pertains
• 14:15
  to
• 14:16
  mania
• 14:16
  or
• 14:16
  psychosis,
• 14:17
  that's
• 14:17
  a
• 14:17
  great
• 14:17
  thing.
• 14:18
  But
• 14:18
  if
• 14:18
  you
• 14:18
  block
• 14:18
  them
• 14:19
  to
• 14:19
  the
• 14:19
  point
• 14:19
  where
• 14:19
  the
• 14:19
  party's,
• 14:20
  like,
• 14:20
  dead
• 14:20
  and
• 14:21
  it
• 14:21
  doesn't
• 14:21
  really
• 14:22
  function
• 14:22
  anymore,
• 14:23
  that's
• 14:23
  when
• 14:24
  you
• 14:24
  might
• 14:24
  be
• 14:24
  more
• 14:24
  interested
• 14:25
  in
• 14:25
  a
• 14:25
  partial
• 14:25
  agonist.
• 14:26
  There's
• 14:26
  a
• 14:26
  lot
• 14:26
  to
• 14:27
  think
• 14:27
  about
• 14:27
  here,
• 14:27
  right?
• 14:28
  Partial
• 14:28
  agonists
• 14:29
  are
• 14:29
  one
• 14:29
  of
• 14:29
  the
• 14:30
  coolest
• 14:30
  mechanisms
• 14:31
  in
• 14:31
  psychopharmacology.
• 14:32
  And
• 14:33
  just
• 14:33
  remember,
• 14:34
  even
• 14:34
  though
• 14:34
  we're
• 14:34
  done
• 14:35
  talking
• 14:35
  about
• 14:35
  this
• 14:35
  today,
• 14:36
  your
• 14:36
  meds
• 14:36
  do
• 14:37
  all
• 14:37
  kinds
• 14:37
  of
• 14:37
  things.
• 14:38
  We
• 14:38
  talked
• 14:38
  about
• 14:39
  that,
• 14:39
  and
• 14:39
  we'll
• 14:39
  talk
• 14:39
  about
• 14:39
  it
• 14:40
  in
• 14:40
  future
• 14:40
  episodes.
• 14:40
  Those
• 14:41
  ion
• 14:41
  channel
• 14:41
  modulators,
• 14:43
  the
• 14:43
  transporters,
• 14:44
  the
• 14:44
  intracellular
• 14:45
  signaling
• 14:46
  cascades
• 14:46
  influenced
• 14:47
  by
• 14:49
  different
• 14:49
  medications,
• 14:50
  you
• 14:50
  may
• 14:50
  choose
• 14:50
  doing
• 14:51
  different
• 14:51
  things.
• 14:51
  And
• 14:51
  they
• 14:52
  really
• 14:52
  matter
• 14:52
  because
• 14:53
  it
• 14:53
  influences
• 14:54
  how
• 14:54
  effective
• 14:55
  your
• 14:55
  medications
• 14:55
  are,
• 14:56
  why
• 14:56
  they're
• 14:56
  effective,
• 14:56
  how
• 14:57
  long
• 14:57
  they're
• 14:57
  effective
• 14:58
  for,
• 14:58
  when
• 14:59
  patients
• 14:59
  can
• 14:59
  expect
• 14:59
  a
• 15:00
  response,
• 15:00
  and
• 15:00
  why,
• 15:01
  if
• 15:01
  you're
• 15:02
  antagonizing
• 15:02
  certain
• 15:03
  circuits,
• 15:03
  you
• 15:03
  might
• 15:04
  also
• 15:04
  have
• 15:04
  to
• 15:05
  anticipate
• 15:06
  some
• 15:07
  effects
• 15:07
  that
• 15:07
  are
• 15:07
  not
• 15:08
  therapeutic.
• 15:08
  We
• 15:08
  talked
• 15:09
  about
• 15:09
  the
• 15:09
  motor
• 15:09
  side
• 15:09
  effects
• 15:10
  when
• 15:10
  you're
• 15:10
  antagonizing
• 15:11
  too
• 15:11
  much
• 15:11
  dopamine
• 15:12
  in
• 15:12
  the
• 15:12
  Niagara
• 15:13
  striatal
• 15:13
  pathway.
• 15:14
  This
• 15:14
  stuff's
• 15:15
  very
• 15:15
  fascinating.
• 15:15
  It's
• 15:16
  very
• 15:16
  fun.
• 15:16
  It
• 15:17
  never
• 15:17
  ends.
• 15:17
  I
• 15:18
  hope
• 15:18
  you
• 15:18
  have
• 15:18
  a
• 15:18
  better
• 15:18
  appreciation
• 15:19
  for
• 15:20
  intrinsic
• 15:21
  activity
• 15:21
  and
• 15:22
  what
• 15:23
  your
• 15:23
  meds
• 15:23
  are
• 15:23
  doing
• 15:24
  and
• 15:24
  why
• 15:24
  it
• 15:24
  might
• 15:24
  make
• 15:25
  sense
• 15:25
  to
• 15:25
  have
• 15:25
  a
• 15:25
  partial
• 15:26
  agonist
• 15:27
  involved
• 15:27
  in
• 15:27
  your
• 15:27
  plan
• 15:28
  of
• 15:28
  care
• 15:28
  and
• 15:29
  an
• 15:29
  antagonist
• 15:30
  at
• 15:30
  certain
• 15:30
  times
• 15:31
  in
• 15:31
  your
• 15:31
  plan
• 15:32
  of
• 15:32
  care
• 15:32
  because
• 15:33
  there's
• 15:33
  a
• 15:33
  time
• 15:33
  and
• 15:34
  place
• 15:34
  for
• 15:34
  everything
• 15:34
  and
• 15:35
  it's
• 15:35
  really
• 15:35
  unique
• 15:35
  how
• 15:36
  all
• 15:36
  this
• 15:36
  is
• 15:36
  done.
• 15:37
  Thank
• 15:37
  you
• 15:37
  all
• 15:37
  for
• 15:37
  tuning
• 15:38
  in.
• 15:38
  We
• 15:38
  appreciate
• 15:39
  every
• 15:39
  one
• 15:40
  of
• 15:40
  you.
• 15:40
  Give
• 15:41
  us
• 15:41
  a
• 15:41
  little
• 15:41
  shout
• 15:41
  out
• 15:42
  on
• 15:42
  Apple
• 15:42
  Podcasts
• 15:43
  that
• 15:43
  helps
• 15:43
  us
• 15:43
  the
• 15:43
  best.
• 15:44
  Give
• 15:44
  us
• 15:44
  five
• 15:44
  stars.
• 15:44
  Write
• 15:45
  a
• 15:45
  little
• 15:45
  comment
• 15:45
  and
• 15:46
  the
• 15:46
  best
• 15:46
  thing
• 15:46
  you
• 15:46
  can
• 15:46
  do
• 15:46
  is
• 15:47
  join
• 15:47
  the
• 15:47
  Patreon
• 15:48
  community
• 15:48
  where
• 15:49
  again
• 15:49
  you
• 15:49
  have
• 15:49
  access
• 15:50
  to
• 15:50
  slide
• 15:50
  decks,
• 15:51
  bonus
• 15:52
  podcast
• 15:52
  episodes.
• 15:53
  Really
• 15:54
  good
• 15:54
  evidence
• 15:54
  based
• 15:54
  tools
• 15:55
  and
• 15:55
  resources
• 15:56
  that
• 15:56
  empower
• 15:57
  you
• 15:57
  to
• 15:57
  pass
• 15:57
  your
• 15:57
  boards
• 15:58
  and
• 15:58
  propel
• 15:59
  your
• 15:59
  practice
• 15:59
  forward.
• 16:00
  Until
• 16:00
  next
• 16:00
  time
• 16:01
  you
• 16:01
  take
• 16:01
  care.
• 16:01
  Bye
• 16:02
  bye.