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Biomedical subjects

Peter Gerner

Publications and source records attributed to Peter Gerner.

23 records · Page 2Linked to original sources
PubMedDate not supplied

Differential block of N-propyl derivatives of amitriptyline and doxepin for sciatic nerve block in rats.

BACKGROUND AND OBJECTIVES: The propyl group of ropivacaine ( N -propyl-2',6'-pipecoloxylidide hydrochloride) could be responsible for conferring some sensory selectivity to this drug. Thus, adding a propyl group to experimental local anesthetics (LAs) (e.g., the tricyclic antidepressants amitriptyline and doxepin) to increase sensory selectivity may be useful. We, therefore, synthesized N -propyl amitriptyline and N -propyl doxepin and investigated a potential predominance of sensory/nociceptive block over motor block (differential block) in a rat sciatic nerve block model. In addition, tetrodotoxin (TTX), a naturally occuring Na + channel blocker, was coinjected to investigate whether it increased block duration. METHODS: A 0.2-mL test dose of N -propyl amitriptyline and N -propyl doxepin, at a concentration of 1, 2.5, 5, and 10 mM, (alone or in combination with TTX at a concentration of 20 microM) was injected by the subfascial sciatic nerve approach. Motor function and sensory function (nociception) were evaluated by the force a rat's hind limb produced when pushing against a balance and the reaction to pinch, respectively. RESULTS: N -propyl amitriptyline and N -propyl doxepin demonstrated prolonged block duration, with N -propyl amitriptyline displaying significant differential block at higher concentrations (5 and 10 mM). The combination of either of these drugs with TTX increased the potency as well as the efficacy. Neurotoxicity commenced at concentrations of 5 to 10 mM. CONCLUSIONS: Detailed histopathologic nerve toxicity evaluations are justified to determine whether N -propyl amitriptyline has potential as a more sensory-selective local anesthetic at lower concentrations or as a predominantly sensory-selective neurolytic agent at higher concentrations.

Amitriptyline↗
PubMedDate not supplied

Efficacy of lidocaine or bupivacaine combined with ephedrine in rat sciatic nerve block.

BACKGROUND AND OBJECTIVES: The adrenergic drug ephedrine inhibits Na(+) current in cultured cells expressing Na(+) channels and provides dose-dependent reversible rat sciatic nerve blockade. The dosage required for peripheral nerve blockade in humans would cause unacceptable cardiovascular side effects. We therefore hypothesized that either lidocaine or bupivacaine would show synergy with ephedrine in a rat sciatic nerve block model, allowing a dose reduction and limiting side effects while improving efficacy. METHODS: Sciatic nerves of anesthetized rats were exposed by lateral incision of the thighs; 0.2 mL of different concentrations of the following drugs was injected sub-fascially: bupivacaine, lidocaine, and ephedrine alone and bupivacaine or lidocaine combined with ephedrine (n=8 per group). After animals recovered from anesthesia, a blinded investigator evaluated motor blockade (push against a balance) and sensory/nociceptive blockade (to pinch of the fifth toe) at predefined time intervals. RESULTS: Ephedrine combined with bupivacaine interacted additively for both motor and sensory blockade, and ephedrine combined with lidocaine interacted antagonistically (sub-additive) for sensory blockade and additively for motor blockade. CONCLUSIONS: A combination of ephedrine with either lidocaine or bupivacaine is unlikely to allow a significant dose reduction because of a lack of synergy. Furthermore, the cardiovascular side effects will limit the maximal tolerable dosage of ephedrine.

Adrenergic Agents↗
PubMedDate not supplied

Topical amitriptyline in healthy volunteers.

BACKGROUND AND OBJECTIVES: The antidepressant amitriptyline is used as an adjuvant in the treatment of a variety of chronic pain conditions. This drug interacts with many receptors and ion channels, such as Na+ channels. In a randomized, double-blinded, and placebo-controlled trial, we investigated whether amitriptyline also is capable of providing cutaneous analgesia when applied topically in 14 healthy volunteers. METHODS: Amitriptyline hydrochloride was prepared as a 45% water/45% isopropanol/10% glycerin solution and titrated to pH 8.5 with sodium hydroxide. Four areas, 2 on each arm, of approximately 1 cm(2) each were marked on the ventral aspect of the upper arm. A piece of gauze, placed on each of the marked areas and affixed to the arm with an occlusive plastic dressing, was saturated via syringe with placebo and amitriptyline solutions (10 mmol/L, 50 mmol/L, and 100 mmol/L). After 1 hour, the dressings and gauze were removed. A 16-G blunt needle was used to grade the pain at the marked area once per hour (1 = complete analgesia, 10 = normal pain sensation). RESULTS: The analgesic effects of 50 mmol/L and 100 mmol/L solutions of amitriptyline were significantly higher than those of the placebo or the 10 mmol/L solution. However, no significant difference was found between the analgesia provided by the placebo solution versus the 10 mmol/L solution or between the 50 mmol/L versus the 100 mmol/L solution. The only side effect observed was a concentration-dependent redness of the skin. CONCLUSIONS: Topically applied amitriptyline is effective as an analgesic in humans. Different vehicles may improve its efficacy and decrease the skin redness observed.

Administration, Cutaneous↗
PubMedDate not supplied

Use of a charged lidocaine derivative, tonicaine, for prolonged infiltration anesthesia.

BACKGROUND AND OBJECTIVES: We tested the hypothesis that the duration of cutaneous anesthesia elicited by the permanently charged compound N-phenylethyl lidocaine (tonicaine) would be longer than that elicited by its parent structure, lidocaine, and that it would be less affected by epinephrine (epi), after subcutaneous injection in rats, as a model for infiltration anesthesia. METHODS: Subcutaneous injections were performed on the shaved dorsal skin of rats with either tonicaine or lidocaine (0.1% or 0.5%, n = 8 in each group) with and without epi (1:200,000). Inhibition of the cutaneous trunci muscle reflex was quantitatively evaluated by a blinded observer by the number of times pinpricks failed to elicit the nocifensive motor response out of a total of 6 pinpricks applied to the injected area. RESULTS: Duration of complete nociceptive blockade in the 0.5% tonicaine and lidocaine groups was 619 +/- 47 and 58 +/- 2 minutes, respectively; duration of full recovery in these groups was 1,106 +/- 19 and 86 +/- 3 minutes, respectively. Epi increased the duration of complete block in the 0.5% tonicaine and lidocaine groups to 750 +/- 13 and 97 +/- 11 minutes, respectively, and the duration of full recovery to 1,185 +/- 13 and 172 +/- 6 minutes, respectively. Skin toxicity was seen only in the 0.5% tonicaine with epi group (3 of 8 rats). CONCLUSIONS: Tonicaine is a substantially longer lasting local anesthetic with a delayed onset of action compared with lidocaine and may be useful in situations where long duration of infiltration block is desirable.

Anesthesia, Local↗