Studies of the Mechanism of Action of Gabapentin and Pregabalin

The original animal pharmacology studies of gabapentin from Goedecke (1981-1984: W Reimann, G. Bartoszyk, and others, unpublished data) included studies of anticonvulsant action in mice, rats, and monkeys and antispasticity effects in animal models with mice, rats, and anesthetized cats. Early mechanism of action work centered on electrophysiological changes in spinal reflexes (W Steinbrecher, 1982, unpublished data) and reduced monoamine neurotransmitter release from brain tissue slices in vitro (W Reimann, E. Schlicker). Also in 1984, a group of pharmacologists at Parke-Davis (P. Boxer, R. Anderson et al., Ann Arbor, MI, unpublished data) studied gabapentin in several preclinical models of spasticity in mice. Gabapentin reduced muscle rigidity and increased locomotor agility (apparently by reducing spinal polysynaptic reflexes) at dosages of 10-100mgkg-1 IP. The results with gabapentin compared favorably with other experimental treatments for spasticity (e.g., baclofen, diazepam). Slightly later, mechanism studies focused on transport of gabapentin by the system L amino acid transporter (which proved to be the main mechanism of gabapentin entry across the gut and also across the blood-brain barrier69'70). However, the lack of pharmacological activity with several system L transporter substrates that lacked high affinity for a2-S (data not shown) soon turned attention to other potential sites of action.

Was this article helpful?

0 0
Dealing With Back Pain

Dealing With Back Pain

Deal With Your Pain, Lead A Wonderful Life An Live Like A 'Normal' Person. Before I really start telling you anything about me or finding out anything about you, I want you to know that I sympathize with you. Not only is it one of the most painful experiences to have backpain. Not only is it the number one excuse for employees not coming into work. But perhaps just as significantly, it is something that I suffered from for years.

Get My Free Ebook

Post a comment