Intravenous procaine as a probe of limbic system activity in psychiatric patients and normal controls

Kellner, Charles H.; Post, Robert M.; Putnam, Frank W.; Cowdry, Rex W.; Gardner, David L.; Kling, Mitchel A.; Minichiello, Marcia D.; Trettau, Joan R.; Coppola, Richard

doi:10.1016/0006-3223(87)90053-9

Cited by 55 publications

(15 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This preliminary study suggests that procaine may have utility as a probe of anterior limbic function in this PTSD population. The subjective responses in our patients were relatively mild in contrast to previously published healthy subject responses, which are much more robust, even at lower procaine doses (Kellner et al, 1987;Parekh et al, 1995;Ketter et al, 1996;Adino et al, 1998). Remarkably, there were no signi®cant autonomic changes as measured by pulse and blood pressure.…”

Section: Discussioncontrasting

confidence: 74%

“…Procaine elicits a very powerful subjective response, including anxiety and sensory distortions in many patients (Kellner et al, 1987). The purpose of this pilot study was to determine if a 1 .…”

Section: Procaine Dosesmentioning

confidence: 99%

“…The following rating scales were given at baseline (5 min before infusion) and 5 min post-procaine (or saline) infusion: (1) SCL-90 Symptom Checklist 90-R (SCL-90-R): This is an objective, wellvalidated scale assessing mood and sensory alterations (Derogatis et al, 1976), (2) the Procaine Scale, developed by Kellner et al (1987), in order to measure changes in mood, cognition, and sensations in response to procaine. This scale is correlated with the measure of Global Severity Index from the SCL-90-R and (3) CAPS-B PTSD Reexperiencing Symptoms.…”

Section: Assessmentsmentioning

confidence: 99%

“…Intravenous procaine produces diverse but robust behavioral responses in humans, ranging from fear to euphoria, often with associated perceptual changes, e.g., auditory or visual hallucinations (Kellner et al, 1987;Parekh et al, 1995;Ketter et al, 1996;Adino et al, 1998). A dose of 0 .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Procaine administration and behavioral responsivity in post-traumatic stress disorder: a pilot study of tolerability

Hamner

Ulmer

Horne

et al. 1999

Hum. Psychopharmacol. Clin. Exp.

View full text Add to dashboard Cite

Procaine, a local anesthetic, selectively activates the anterior limbic region of the brain, including the anterior cingulate, and may produce powerful emotional and other behavioral responses (including psychotic symptoms) in humans. In a pilot study, we administered intravenous procaine and placebo (saline) to nine combat veterans with PTSD at a dose of procaine known to produce signi®cant behavioral responses in healthy subjects (1 . 38 mg/kg). All but one PTSD patient had mild to moderate, subjective responses to procaine that were statistically elevated on a procaine symptom rating scale ( p 5 0 . 01) compared with saline. Symptoms that occurred only during the procaine infusion included anxiety or euphoria, auditory and visual hallucinations or illusions, and certain physical symptoms such as paresthesias. Two of the nine patients had speci®c PTSD reexperiencing symptoms. However, all patients tolerated the procedure well and, in eight of the patients, symptoms resolved within 5±10 min of procaine administration. One patient had possible dissociative symptoms up to 1 h after procaine that resolved without a recurrence. No patient had a persistent exacerbation of PTSD symptoms. This pilot study suggests that procaine may be a feasible pharmacologic probe to test anterior limbic function in PTSD.

show abstract

Section: Discussioncontrasting

confidence: 74%

Section: Procaine Dosesmentioning

confidence: 99%

Section: Assessmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Procaine administration and behavioral responsivity in post-traumatic stress disorder: a pilot study of tolerability

Hamner

Ulmer

Horne

et al. 1999

Hum. Psychopharmacol. Clin. Exp.

View full text Add to dashboard Cite

show abstract

“…in healthy volunteers (Kellner et al, 1987), results in brief intense emotional (ranging from euphoria to dysphoria) and sensory experiences (visual, auditory, and olfactory illusions/hallucinations) in association with increased relative anterior paralimbic cerebral blood flow (CBF) as measured with [ 15 O] water positron emission tomography (PET) (Ketter et al, 1996). In healthy individuals, procaine also induces the following: hormonal changes such as increased adrenocorticotropic hormone (ACTH), cortisol, and prolactin (Kling et al, 1994); and increased temporal lobe fast activity electroencephalogram (EEG) (Parekh et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

A Potential Cholinergic Mechanism of Procaine's Limbic Activation

Benson

Carson

Kiesewetter

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

The local anesthetic procaine, when administered to humans intravenously (i.v.), yields brief intense emotional and sensory experiences, and concomitant increases in anterior paralimbic cerebral blood flow, as measured by positron emission tomography (PET). Procaine's high muscarinic affinity, together with the distribution of muscarinic receptors that overlaps with brain regions activated by procaine, suggests a muscarinic contribution to procaine's emotional and sensory effects. This study evaluates the effects of procaine on cerebral muscarinic cholinergic receptors in the anesthetized rhesus monkey. Whole brain and regional muscarinic receptor binding was measured before and after procaine administration on the same day in three anesthetized rhesus monkeys with PET and the radiotracer 3-(3-(3[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([ 18 F]FP-TZTP), a cholinergic ligand that has preferential binding to muscarinic (M 2 ) receptors. On separate days each animal received six different doses of i.v. procaine in a randomized fashion. Procaine blocked up to B90% of [ 18 F]FP-TZTP specific binding globally in a dose-related manner. There were no regional differences in procaine's inhibitory concentration for 50% blockade (IC 50 ) for [ 18 F]FP-TZTP. Tracer delivery, which was highly correlated to cerebral blood flow in previous monkey studies, was significantly increased at all doses of procaine with the greatest increases occurring near procaine's IC 50 for average cortex. Furthermore, anterior limbic regions showed greater increases in tracer delivery than nonlimbic regions. Procaine has high affinity to muscarinic M 2 receptors in vivo in the rhesus monkey. This, as well as a preferential increase of tracer delivery to paralimbic regions, suggests that action at these receptors could contribute to i.v. procaine's emotional and sensory effects in man. These findings are consistent with other evidence of cholinergic modulation of mood and emotion.

show abstract

Anterior Paralimbic Mediation of Procaine-Induced Emotional and Psychosensory Experiences

Ketter

Andreason

George

et al. 1996

Arch Gen Psychiatry

186

View full text Add to dashboard Cite

show abstract

Intravenous procaine as a probe of limbic system activity in psychiatric patients and normal controls

Cited by 55 publications

References 65 publications

Procaine administration and behavioral responsivity in post-traumatic stress disorder: a pilot study of tolerability

Procaine administration and behavioral responsivity in post-traumatic stress disorder: a pilot study of tolerability

A Potential Cholinergic Mechanism of Procaine's Limbic Activation

Anterior Paralimbic Mediation of Procaine-Induced Emotional and Psychosensory Experiences

Contact Info

Product

Resources

About