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PubMed1997

The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial.

Seventy-two patients older than 60 years of age who received a diagnosis of herpes zoster (HZ) were entered into a randomized, double-blind, placebo-controlled trial of daily amitriptyline 25 mg. Treatment with either amitriptyline or placebo continued for 90 days after diagnosis. Pain prevalence at 6 months was the primary outcome. Results showed that early treatment with low-dose amitriptyline reduced pain prevalence by more than one-half (p < 0.05; odds ratio, 2.9:1) This finding makes a strong case for the pre-emptive administration of amitriptyline, in combination with an antiviral drug, to elderly patients with acute herpes zoster.

Adrenergic Uptake Inhibitors↗
PubMed2002

Role of Gi proteins in the antidepressant-like effect of amitriptyline and clomipramine.

The effect of the i.c.v. administration of pertussis toxin (PTX) and antisense oligodeoxynucleotides directed against the alpha subunit of different Gi-proteins (anti-Gi alpha(1), anti-Gi alpha(2), anti-Gi alpha(3), anti-Go alpha(1), anti-Go alpha(2)) on the antidepressant-like effect induced by amitriptyline and clomipramine, was evaluated in the mouse forced swimming test, an animal model of depression. The administration of amitriptyline (15 mg kg(-1) s.c.) and clomipramine (25 mg kg(-1) s.c.) produced an increase in the mobility time that was prevented by PTX (0.25 micro g per mouse i.c.v.), administered 11 days before the mouse forced swimming test. Anti-Gi alpha(1) (12.5 micro g per mouse i.c.v.), anti-Gi alpha(2) (12.5 micro g per mouse i.c.v.), anti-Gi alpha(3) (6.25 micro g per mouse i.c.v.), and anti-Go alpha(1) (6.25 micro g per mouse i.c.v.), administered 24 and 18 h before the training session, prevented the amitriptyline and clomipramine increase of the mobility time. By contrast, pretreatment with anti-Go alpha(2) (1.56-12.5 micro g per mouse i.c.v.) never modified the antidepressant-like effect induced by the two investigated compounds. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota-rod test, nor modified spontaneous motility and inspection activity, as revealed by the hole-board test. These results suggest the important role played by Gi(1), Gi(2), Gi(3), and Go(1) protein subtypes and the lack of involvement by Go(2) protein subtype in the transduction mechanism responsible for the antidepressant-like effect produced by amitriptyline and clomipramine.

Amitriptyline↗
PubMed1997

Pharmacological treatment of severely depressed patients: a meta-analysis comparing efficacy of mirtazapine and amitriptyline.

Efficacy data were available from 405 severely depressed patients (baseline 17-item Hamilton Rating Scale for Depression-HAMD scores > or = 25) participating in randomized, double-blind, amitriptyline-controlled studies of mirtazapine. Main efficacy variable were changes from baseline in the group mean 17-item HAMD scores and responder rates. Secondary efficacy variables were changes in depressed mood item on the HAMD and in factors derived from the 17-item HAMD scale. Treatment with either mirtazapine or amitriptyline resulted in robust reductions of baseline HAMD scores and in similar and high percentages of responders. Both drugs produced favourable effects on depressed mood and on symptoms commonly associated with depression, such as anxiety, sleep and vegetative disturbances. There were neither statistically significant nor clinically relevant differences between mirtazapine and amitriptyline at any assessment point nor at endpoint. The results demonstrate that the new antidepressant mirtazapine and the tricyclic antidepressant amitriptyline are equally effective in the treatment of severely depressed patients.

Adolescent↗
PubMed1991

Identifying the specific clinical actions of amitriptyline: interrelationships of behaviour, affect and plasma levels in depression.

Despite increasing knowledge of the neurochemical bases of the action of the tricyclic drugs, little is known about the sequence of psychological effects which precede recovery in drug-responsive patients. This research was aimed at identifying the specific behavioural effects associated with the therapeutic action of amitriptyline in depression. The design involved measurement (post-hoc) of weekly changes in a severely depressed placebo-resistant group who recovered with drug treatment, compared with a group of similar patients treated for the equivalent four weeks, who showed minimal to no clinical response. The research strategy, in accordance with a dose-response paradigm, was to determine which of the early changes in emotion and behaviour found in treatment responders were systematically associated with plasma concentrations of amitriptyline or its major metabolite. Amitriptyline was found to act within seven days on the components of anxiety and on hostility in the responders, and on sleep disorder in all patients. After 12 to 14 days of treatment these effects increased, with improvements in other significant components distinguishing the responders from the non-responders. At the 12th to 14th treatment days when a steady state concentration of drug in plasma was approached, reductions in anxiety and hostility and in certain somatic components correlated significantly with plasma concentrations of amitriptyline. Implications of the findings for clarifying the specificity of clinical actions of the tricyclic drugs, and for understanding the psychobiological dynamics underlying rapid drug-induced recovery in depression, were explored.

Affect↗
PubMed2001

Treatment of depression in patients with breast cancer: a comparison between paroxetine and amitriptyline.

In the context of chronic physical illness, such as breast cancer, depression is associated with increased morbidity, longer periods of hospitalization, and greater overall disability. Prompt diagnosis and effective treatment is. therefore, essential. Several small studies have established the efficacy of tricyclic antidepressants (TCAs) in this setting, and the selective serotonin reuptake inhibitors (SSRIs) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile. This was a multicenter. double-blind, parallel-group study in which 179 women with breast cancer were randomized to treatment with either the SSRI paroxetine (20-40 mg/day), or the TCA, amitriptyline (75-150 mg/day). After 8-weeks treatment, depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale. Clinical global impression (CGI) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint: a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale. A steady improvement in quality of life was also observed in both groups. There were no clinically significant differences between the groups. In total, 47 (53.4%) patients in the paroxetine group and 53 (59.6%) patients in the amitriptyline group had adverse experiences, the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy. Anticholinergic effects were almost twice as frequent in the amitriptyline group (19.1%) compared with paroxetine (11.4%). This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer.

Adult↗
PubMed2002

Amitriptyline inhibits voltage-sensitive sodium currents in rat gastric sensory neurons.

Recent studies indicate that peripheral mechanisms contribute to the analgesic effect of amitriptyline. We hypothesized that amitriptyline inhibits voltage-dependent sodium currents in gastric sensory neurons. To label gastric neurons, the stomach was exposed in male Sprague Dawley rats through a midline incision to inject the retrograde tracer DiI into the gastric wall. Seven days after surgery, nodose ganglia were harvested. Neurons were dissociated and cultured for 4-24 hr to record whole cell sodium currents with the patch-clamp technique. Amitriptyline reversibly inhibited voltage-sensitive sodium currents with an IC50 of 20 microM. At clinically relevant concentrations, the peak sodium current decreased by about 15%. This was associated with a slowed recovery from inactivation, leading to a significantly enhanced cumulative inhibition during brief repetitive depolarizations. These findings are consistent with a use-dependent block of voltage-dependent sodium channels by amitriptyline. This effect may contribute to the analgesic properties of tricyclic antidepressants.

Amitriptyline↗
PubMed1980

Effect of amitriptyline antidotes on repetitive extrasystole threshold.

The effect of amitriptyline that leads to ventricular tachycardia was evaluated by the repetitive extrasystole threshold (RET) technique in 18 dogs. The RET was 28.8 +/- 7.9 mamp before and 8.2 +/- 5.3 mamp after amitriptyline, p less than 0.001. Physostigmine, propranolol, sodium bicarbonate, and left stellate ganglionectomy reversed the effect of amitriptyline on RET. We conclude that amitriptyline overdose predisposes to sudden death by lowering the ventricular fibrillation threshold. This cardiotoxic effect is mediated partly through the central nervous system and can be inhibited by increased plasma binding (bicarbonate), cholinergic stimulation (physostigmine), beta adrenergic blockade (propranolol), and sympathetic denervation (left stellate ganglionectomy).

Amitriptyline↗
PubMed1999

Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline.

1 Tricyclic antidepressants (TCAs) are associated with cardiovascular side effects including prolongation of the QT interval of the ECG. In this report we studied the effects of two TCAs (imipramine and amitriptyline) on ionic current mediated by cloned HERG potassium channels. 2 Voltage clamp measurements of HERG currents were made from CHO cells transiently transfected with HERG cDNA. HERG-encoded potassium channels were inhibited in a reversible manner by both imipramine and amitriptyline. HERG tail currents (IHERG) following test pulses to +20 mV were inhibited by imipramine with an IC50 of 3.4+/-0.4 microM (mean+/-s.e.mean) and a Hill coefficient of 1.17+/-0.03 (n = 5). 3 microM amitriptyline inhibited IHERG by 34+/-6% (n = 3). The inhibition showed only weak voltage dependence. 3 Using an 'envelope of tails' comprised of pulses to +20 mV of varying durations, the tau of activation was found to be 155+/-30 ms for control and 132+/-26 ms for 3 microM imipramine (n = 5). Once maximal channel activation was achieved after 320 ms (as demonstrated by maximal tail currents), further prolongation of depolarization did not increase imipramine-mediated HERG channel inhibition. 4 Taking current measurements every second during a 10 s depolarizing pulse from -80 mV to 0 mV, block was observed during the first pulse in the presence of imipramine and the level of IHERG block was similar throughout the pulse (n=5). 5 A three pulse protocol (two depolarizing pulses to +20 mV separated by 20 ms at -80 mV) revealed that imipramine did not significantly alter the kinetics of IHERG inactivation. The tau of inactivation was 8+/-2 ms and 5.6+/-0.4 ms (n = 5) in the absence and presence of 3 microM imipramine, respectively, and currents inactivated to a similar extent. 6 Our data are consistent with TCAs causing components of block of the HERG channel in both the closed and open states. Any component of open channel block occurs rapidly upon depolarization. Inhibition of IHERG by the prototype TCAs imipramine and amitriptyline may suggest a mechanism for QT prolongation associated with risks of arrhythmia and sudden death that accompany high concentrations of TCAs following overdose.

Amitriptyline↗
PubMedDate not supplied

Effects of amitriptyline and fluoxetine upon the in vitro proliferation of tumor cell lines.

Previous publications have suggested that commonly prescribed antidepressants have the potential to stimulate the proliferation of extant tumors in human and rodent in vivo and in vitro models. The direct effects of amitriptyline and fluoxetine were evaluated in assays that detect different aspects of proliferative responses at pharmacologically relevant drug concentrations. Three in vitro assays of cellular proliferation and clonal growth were used with human (MCF7, PA-1 and LS174T) and murine (B16.f10, C-3 and B16.f1) tumor cell lines. The cells were exposed to amitriptyline or fluoxetine (0.001-100 microM) for different time periods (1-7 days) and at varying serum concentrations (0.1-15%). Amitriptyline and fluoxetine failed to significantly stimulate tumor cell proliferation, DNA synthesis, or colony formation. Both drugs inhibited B16.f10 colony growth at concentrations above 5 microM along with significant suppression of DNA synthesis in B16.f10 and C-3 cells at 30 microM. Although there were generally no effects on cell proliferation by the drugs in the microtiter tetrazolium assay, several rare instances of stimulation were noted. Amitriptyline and fluoxetine were consistent in their lack of effect or inhibition with the human or murine tumor cell lines in conventional in vitro assays of cell proliferation and clonogenicity in optimal or suboptimal culture conditions.

Amitriptyline↗
PubMed2003

Treating chronic tension-type headache not responding to amitriptyline hydrochloride with paroxetine hydrochloride: a pilot evaluation.

CONTEXT: In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. OBJECTIVE: To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. DESIGN AND SETTING: Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. PARTICIPANTS AND INTERVENTION: Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. OUTCOME MEASURES: Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. RESULTS: In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. CONCLUSIONS: We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo.

Adult↗
PubMed1990

Double-blind study of the therapeutic efficacy and tolerability of amitriptylinoxide in comparison with amitriptyline.

In a double-blind trial, 32 patients with endogenous or neurotic depression requiring drug treatment in hospital were randomly allocated to a four-week treatment with amitriptylinoxide or amitriptyline. The initial dosage was, in most cases, 60 mg b.i.d. for both drugs. During the first week of treatment, the dose was increased to a maximum of 300 mg/day with amitriptylinoxide and to 240 mg/day with amitriptyline, depending on tolerability and clinical impression. This dose was then maintained, if possible, throughout the following three weeks. During this period the mean dose of amitriptylinoxide was 167 +/- 8 mg/day, that of amitriptyline 166 +/- 8 mg/day. Seven of the 32 patients (three in the amitriptylinoxide and four in the amitriptyline group) discontinued the trial. Therapeutic efficacy was assessed by means of the AMDP system (scale 4), HAMD total scale, 4 HAMD subscales, and DSI and Bf-S scales. Tolerability was assessed using the AMDP system (scale 5) and a list of side-effects often associated with antidepressive drug treatment. With regard to therapeutic efficacy, no differences were noted between the two drugs except on the DSI scale. In contrast, there was a significant difference in tolerability--both in terms of the vegetative syndrome (AMDP) and the sum of side-effects--in favour of amitriptylinoxide.

Adult↗
PubMed1980

Amitriptyline, nortriptyline plasma levels and clinical response in women with affective disorders.

The relationship between the plasma levels of amitriptyline and its metabolite nortriptyline, as well as their side-effects and clinical response, were studied in 102 depressed female in-patients, treated with different dosages of amitriptyline. For 50 and 100 mg dosages, significant positive correlations were found between amitriptyline concentration and the Hamilton amelioration scores, as well as between Hamilton final values and side effects. For depressive neurosis and involutional melancholia best therapeutic responses were yielded at a dosage of 50 mg, while in the treatment of manic-depressive illness, comparable results occurred at a 150 mg dosage. In the depressive neurosis and in the involutional melancholia the upper plasma concentration limits for the therapeutic effect of nortriptyline were identified. The lower plasma concentration limits of amitriptyline and nortriptyline in the treatment of manic-depressive illness were also pointed out.

Adjustment Disorders↗
PubMed1996

Low serum levels of tricyclic antidepressants in amitriptyline- and doxepin-treated inpatients with depressive syndromes are associated with nonresponse.

Nonresponse to tricyclic antidepressant (TCA) treatment is observed in about one-third of depressed patients. The cause(s) for nonresponse - apart from disease-specific effects - might be the failure to build up sufficiently high serum TCA levels due to noncompliance, substance abuse, rapid metabolism, or low dose. We carried out a retrospective analysis relating antidepressant serum levels to patient data obtained in the naturalistic setting of the Psychiatric Hospital of the Bonn University during the introductory phase of drug-monitoring. Case reports of 110 depressed inpatients who were treated with amitriptyline or doxepin were analyzed with respect to the following: medication and comedication, daily dose, type and duration of treatment, serum TCA concentrations (analyzed by the fluorescence polarization immunoassay), age, sex, body weight, abuse of nicotine or alcohol intake, serum transaminases (ALT, alanine aminotransferase, and AST, aspartate amino transferase), gamma-glutamyltranspeptidase (gamma-GT) and creatinine, compliance, and response. The salient findings were: 1. Serum TCA concentrations increased linearly with the daily amitriptyline dose but not with that of doxepin. 2. Interindividually, there was an eight to ten-fold difference in serum TCA concentrations at steady-state with 150 mg/day of either drug; longitudinally, we observed intraindividually a coefficient of variation of 8% and 12% for amitriptyline and doxepin respectively. 3. With amitriptyline (150 mg/day), the correlation between age and serum TCA concentrations was low (r = 0.33, p < 0.055) and no correlation was found after the administration of doxepin (150 mg/day), nor was there any correlation between age and dose-adjusted serum TCA concentrations after the administration of either drug. 4. Nonresponders had significantly lower serum levels than responders. These results suggest that patients should not qualify as nonresponders unless it can be demonstrated (and it is clinically applicable) that the steady-state serum TCA levels are stable within the upper limit of the recommended therapeutic range and serum level.

Adult↗
PubMed2001

The effect of four-week administration of amitriptyline on sleep bruxism. A double-blind crossover clinical study.

The purpose of this study was to evaluate the effect of a tricyclic antidepressant (amitriptyline) on nocturnal masseteric activity and duration of sleep in bruxists. Using a randomized, double blind, crossover design, ten females (mean age 39 yrs, +/- sd seven yrs) received active (amitriptyline 25 mg/night) and inactive (placebo 25 mg/night) medication, over a period of four weeks each. A portable EMG integrator recorded the nocturnal, unilateral, and cumulative myoelectrical activity (microV/min of sleep) of the masseter muscle during the fourth and eighth weeks of the study. The results showed that amitriptyline did not significantly decrease the mean EMG activity (df = 9, alpha = 0.05, paired-t = 0.892, p = 0.3964), nor did it significantly increase the duration of sleep (df = 9, alpha = 0.05, paired-t = 2.140, p = 0.061). The results of this study do not support the administration of 25 mg of amitriptyline per night over a period of four weeks for the management of sleep bruxism.

Adult↗
PubMed1988

Effects of naloxone and verapamil in experimental amitriptyline poisoning in rats.

The effects of verapamil and naloxone as potential antidotes for amitriptyline-induced cardiotoxicity were investigated in an experimental rat model. Amitriptyline was infused continuously at a dose of 37.5 mg/kg/h. After 15 minutes, the animals were given either naloxone (2 mg/kg + 3 mg/kg/h), verapamil (0.08 mg/kg + 0.08 mg/kg/h), or physiological saline. In the group given naloxone, a significant decrease in heart rate was seen. Although MAP and max dP/dT increased, there was no significant difference from controls. Naloxone did not decrease mortality. When the bolus dose of verapamil was given, a significant decrease in MAP and max dP/dT was obtained. Although the mean blood pressure was significantly higher in those animals treated with verapamil who survived 60 minutes, verapamil did not change the course of the amitriptyline poisoning. In conclusion, our findings indicate that naloxone lacks significant positive effects and that verapamil has an additional negative inotropic effect. Neither drug can be recommended for the treatment of amitriptyline poisoning.

Amitriptyline↗
PubMed1997

Amitriptyline accumulation and elimination in Calliphora vicina larvae.

Calliphora vicina larvae reared on artificial foodstuffs spiked with human equivalent therapeutic (100 ng/g), toxic (300 ng/g), lethal (500 ng/g), and 10 x lethal (5,000 ng/g) concentrations of amitriptyline and nortriptyline, alone and in various combinations, were harvested at various stages of development and analysed for drug content by high-pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Mean (range) larval amitriptyline concentrations (ng/g) in larvae reared on foodstuffs containing 100 ng/g, 500 ng/g, and 5,000 ng/g amitriptyline were 3.21 (<1-5.72), 21.3 (14.2-27.4), and 50.1 (38.8-64.3), respectively, on day 5; 6.62 (5.98-7.72), 22.5 (16.4-32.4), and 38 (22.8-50.9) on day 8; and 4.45 (3.45-5.93), 25.2 (18.6-38.4), and 26.2 (22.7-29.7) on day 11. Nortriptyline concentrations (ng/g) in larvae reared on foodstuffs containing 100 ng/g, 500 ng/g, and 5,000 ng/g nortriptyline were 6.86 (4.48-8.96), 14.1 (11.9-17.8), and 18.5 (16.7-20.6), respectively, on day 5; 8.32 (4.9-11.7), 12.9 (11.5-14.2), and 18.8 (11.5-23) on day 8; and 5.06 (3.27-7.25), 19.4 (17.8-22.4), and 26.6 (11.7-44.7) on day 11. Among 45 separate larval rearings fed on the same foodstuff, mean larval weight ranged from 24-96 mg and larval amitriptyline concentration from <1-148 ng/g. Biological variability in larval drug concentrations were greatest in larvae reared on high drug concentrations. Such variability makes quantitative extrapolation back to the drug concentration in foodstuff unreliable. Larval drug accumulation became unpredictable when larvae encounter more than one drug or different concentrations of a single drug. Drug concentrations measured were partly due to surface contamination with drug-rich putrefactive residue and they also depend partly on the analytical method used. Fly larvae are unreliable samples for quantitative toxicological analysis.

Administration, Oral↗
PubMed2002

The effect of local anesthetics and amitriptyline on peroxidation in vivo in an inflammatory rat model: preliminary reports.

We studied the inhibition of peroxidation by local anesthetics in an inflammatory animal model. Inflammatory lipid peroxidation was assessed by the thiobarbituric assay in plasma from rats injected or not injected with carrageenan (Carra) and killed 1, 2, 4, 6, 12, and 24 h thereafter. Thiobarbituric acid reactive substances (TBARS) values in inflammatory animals were maximal 6 h after Carra administration. This result, in accordance with the evolution of paw edema width during time, supports that TBARS reflect the intensity of inflammation. Local anesthetics (bupivacaine, lidocaine, ropivacaine, or bupivacaine-loaded microspheres) or amitriptyline were injected in clinically relevant concentrations as a sciatic nerve block or intraperitoneally in inflamed animals. Ropivacaine did not exhibit any protective effect on Carra-induced lipid peroxidation in rats. With all the other drugs administered as a sciatic nerve block, the maximal TBARS increase was not observed at 6 h. Our conclusion is that bupivacaine (plain or encapsulated), lidocaine, and amitriptyline in clinically relevant concentrations administered via the sciatic nerve showed antioxidant properties toward lipid peroxidation induced by Carra inflammation. Intraperitoneal injection of those drugs gave the same effect as nerve block; this result suggests that their mechanism of action is not strictly limited to the nerve. IMPLICATIONS. We investigated the antioxidant effects of local anesthetics and amitriptyline in an inflammatory rat model. Amitriptyline exhibits antioxidant properties per se, whereas lidocaine and bupivacaine (plain or encapsulated) seem to inhibit the peroxidation process. This may have future application in limiting toxic oxygen metabolite production during the inflammatory process.

Amides↗
PubMed1995

Intrathecal amitriptyline. Antinociceptive interactions with intravenous morphine and intrathecal clonidine, neostigmine, and carbamylcholine in rats.

BACKGROUND: Systemically administered opioids induce analgesia in part by spinal noradrenergic, serotonergic, and cholinergic mechanisms. The current study tested whether antinociception from systemically administered opioids could therefore be enhanced by intrathecal injection of a monoamine reuptake inhibitor to potentiate the action of spinally released norepinephrine and serotonin (amitriptyline) and intrathecal injection of a cholinesterase inhibitor to potentiate the action of spinally released acetylcholine (neostigmine). METHODS: Rats were prepared with chronic lumbar intrathecal and femoral intravenous catheters and nociceptive threshold was assessed by hind paw withdrawal to a radiant heat stimulus. An isobolographic design was used to distinguish between additive and synergistic interactions. RESULTS: Intravenous morphine and intrathecal neostigmine, but not intrathecal amitriptyline, caused dose-dependent antinociception alone. Combining any two of these three treatments yielded a synergistic interaction compared to each alone, whereas combining all three yielded an additive interaction compared to each two-way interaction. Intrathecal amitriptyline did not affect antinociception from intrathecal clonidine or intrathecal carbamylcholine. CONCLUSIONS: These data suggest that intrathecal doses of amitriptyline resulting in potentiation of intravenous morphine antinociception may not be adequate to block muscarinic receptors, because they did not affect carbamylcholine-induced antinociception. These results further support the relevance of spinal monoamine reuptake and cholinesterase inhibition to synergistically enhance analgesia from systemic opioids.

Adrenergic Agents↗