Phase 1A Safety Assessment of Intravenous Amitriptyline

Fridrich, Peter; Colvin, Hans Peter; Zizza, Anthony M.; Wasan, Ajay D.; Lukanich, Jean; Lirk, Philipp; Saria, Alois; Zernig, Gerald; Hamp, Thomas; Gerner, Peter

doi:10.1016/j.jpain.2007.02.433

Cited by 15 publications

(12 citation statements)

References 36 publications

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“…This dosage has been demonstrated to be safe for intravenous administration in a recent clinical study. 26 In this study, preoperative intravenous infusion of amitriptyline over 1 hour appeared to be safe at a dose of 50 mg as assessed by QTc interval, adverse effects monitoring, and measurements of plasma levels of amitriptyline and nortriptyline. Similarly, our experience from treating patients with a wound chamber confirms the observation that high dosages of antibiotics can be administered topically without systemic toxicity.…”

Section: Discussionmentioning

confidence: 72%

Safety Evaluation of Topically Applied Amitriptyline in Porcine Full-Thickness Wounds

Pomahac

Zuhaili

Kudsi

et al. 2007

Regional Anesthesia and Pain Medicine

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Section: Discussionmentioning

confidence: 72%

Safety Evaluation of Topically Applied Amitriptyline in Porcine Full-Thickness Wounds

Pomahac

Zuhaili

Kudsi

et al. 2007

Regional Anesthesia and Pain Medicine

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“…Amitriptyline is sometimes used as an alternative following lidocaine. 20 Herein, we report detailed clinical and genetic investigation of a family with PEPD caused by a novel mutation in the SCN9A gene; in vitro electrophysiological evidence of pathogenicity; and effects of amitriptyline and cold exposure both at the clinical and electrophysiological levels.…”

Section: Pain Medicinementioning

confidence: 99%

p.L1612P, a Novel Voltage-gated Sodium Channel Nav1.7 Mutation Inducing a Cold Sensitive Paroxysmal Extreme Pain Disorder

et al. 2015

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Background: Mutations in the SCN9A gene cause chronic pain and pain insensitivity syndromes. We aimed to study clinical, genetic, and electrophysiological features of paroxysmal extreme pain disorder (PEPD) caused by a novel SCN9A mutation. Methods: Description of a 4-generation family suffering from PEPD with clinical, genetic and electrophysiological studies including patch clamp experiments assessing response to drug and temperature. Results: The family was clinically comparable to those reported previously with the exception of a favorable effect of cold exposure and a lack of drug efficacy including with carbamazepine, a proposed treatment for PEPD. A novel p.L1612P mutation in the Nav1.7 voltage-gated sodium channel was found in the four affected family members tested. Electrophysiologically the mutation substantially depolarized the steady–state inactivation curve (V1/2 from −61.8 ± 4.5 mV to −30.9 ± 2.2 mV, n = 4 and 7, P < 0.001), significantly increased ramp current (from 1.8% to 3.4%, n = 10 and 12) and shortened recovery from inactivation (from 7.2 ± 5.6 ms to 2.2 ± 1.5 ms, n = 11 and 10). However, there was no persistent current. Cold exposure reduced peak current and prolonged recovery from inactivation in wild-type and mutated channels. Amitriptyline only slightly corrected the steady–state inactivation shift of the mutated channel, which is consistent with the lack of clinical benefit. Conclusions: The novel p.L1612P Nav1.7 mutation expands the PEPD spectrum with a unique combination of clinical symptoms and electrophysiological properties. Symptoms are partially responsive to temperature but not to drug therapy. In vitro trials of sodium channel blockers or temperature dependence might help predict treatment efficacy in PEPD.

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“…Alternatively, AM is a potent local anesthetic with longer effect compared with bupivacaine 9 . The analgesic effect of AM is most likely caused by blocking of Na + channels 8 . So therefore, we aimed to evaluate the analgesic effect of AM mucoadhesive tablet as a topical dosage form.…”

Section: Buccal Analgesic Efficiencymentioning

confidence: 99%

“…The analgesic effect of tricyclic antidepressant medicines seems unrelated to their antidepressant action as the doses used for analgesia are lower than those considered effective in the treatment of depression [1][2][3][4][5][6][7] . The analgesic effect of AM is almost certainly due to blocking of Na + channels 8 . Further experimentation has shown that AM is indeed a potent local anesthetic with longer effect compared with bupivacaine 9 .…”

Section: Introductionmentioning

confidence: 99%

Development of amitriptyline buccoadhesive tablets for management of pain in dental procedures

Movassaghian¹,

Barzegar-Jalali²,

Alaeddini³

et al. 2011

Drug Development and Industrial Pharmacy

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Administration of lidocaine and nonsteroidal anti-inflammatory drugs (NSAIDs) as a routine procedure for relief of dental pains by and large is restricted due to some side effects. Amitriptyline (AM) has long been known to exert analgesic activity as a result of blocking the Na⁺ channels. The objective of the present investigation was to prepare suitable buccoadhesive tablets using cellulose derivatives in order to obtain new formulations containing AM to provide local analgesic action. The tablets were evaluated in terms of physical characteristics, mucoadhesion performance, drug release, and in vivo assessment of analgesic efficiency. Tablets containing higher amounts of high-viscosity hydroxypropylmethyl cellulose (HPMC-K4M) significantly demonstrated enhanced adhesive performances. On the other hand, presence of sodium carboxymethyl cellulose (NaCMC) in formulations including HPMC of lower-viscosity grade (HPMC-E5LV) provided further adhesiveness by increase in viscosity. Rate of drug release from HPMC-E5LV tablets was significantly higher than the HPMC-K4M tablets. Kinetically, patterns of AM release from the tablets fitted best to Higuchi model. Moreover, in a randomized double-blind trial, analgesic efficiency of the prepared bioadhesive tablets was revealed to be satisfactory. It is suggested that applying the topical AM mucoadhesive tablet containing the low amount of drug is a safe and promising alternative to relief the pain in the buccal region.

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Phase 1A Safety Assessment of Intravenous Amitriptyline

Cited by 15 publications

References 36 publications

Safety Evaluation of Topically Applied Amitriptyline in Porcine Full-Thickness Wounds

Safety Evaluation of Topically Applied Amitriptyline in Porcine Full-Thickness Wounds

p.L1612P, a Novel Voltage-gated Sodium Channel Nav1.7 Mutation Inducing a Cold Sensitive Paroxysmal Extreme Pain Disorder

Development of amitriptyline buccoadhesive tablets for management of pain in dental procedures

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