Biomedical subjects

Mustafa Mujtaba

Publications and source records attributed to Mustafa Mujtaba.

2 recordsLinked to original sources

PubMed2003

Assessment of differential blockade by amitriptyline and its N-methyl derivative in different species by different routes.

BACKGROUND: Increasing the duration of local anesthesia and/or creating greater differential blockade (i.e., selective block of pain-transmitting nerve fibers) has been attempted by modifying currently available agents. Most drugs show a different profile depending on the model or species studied. This study was designed to investigate the differential nerve-blocking properties of amitriptyline and its quaternary ammonium derivative in rats and sheep. METHODS: The Na+ channel-blocking properties of N-methyl amitriptyline were determined with the patch clamp technique in cultured GH(3) cells. Various functions (motor, nociception, proprioception-ataxia) were compared in rats (spinal and sciatic nerve blockade) and sheep (spinal blockade) with amitriptyline, N-methyl amitriptyline, lidocaine, and bupivacaine (partially from historical data). RESULTS: In vitro testing revealed N-methyl amitriptyline to be a potent Na+ channel blocker similar to amitriptyline but with a much longer duration of action. All drug concentrations tested in both the sciatic nerve model and the spinal block model produced no significant differential blockade in rats. Three of six rats in the 20-mM N-methyl amitriptyline group showed residual blockade 4 days after sciatic nerve injection. However, in the sheep spinal model, amitriptyline and in particular N-methyl amitriptyline displayed significant differential blockade at most time points. Sheep data for lidocaine and bupivacaine seemed to be more comparable to the clinical experience in humans than did rat data. CONCLUSIONS: Amitriptyline and N-methyl amitriptyline are potent Na+ channel blockers and show greater differential blockade in sheep than in rats. This differential blockade in sheep is greater than that produced by lidocaine or bupivacaine.

Amitriptyline↗

PubMed2002

N-phenylethyl amitriptyline in rat sciatic nerve blockade.

BACKGROUND: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na(+) channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties. METHODS: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH(3) cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model. RESULTS: In vitro, N-phenylethyl amitriptyline at 10 microm elicits a greater block of Na(+) channels than amitriptyline (resting block of approximately 90% vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm. CONCLUSION: N-phenylethyl amitriptyline appears to have a narrow therapeutic range but is much more potent than lidocaine, providing a block duration several times longer than any clinically used local anesthetic. Further work in animal models of neuropathic pain will assess the potential use of this drug.

Amitriptyline↗