Posted by zeugma on February 27, 2006, at 16:57:26
In reply to Re: provigil discussion » mike99, posted by Larry Hoover on February 27, 2006, at 10:41:03
Then you get to drugs like modafinil, where no one has a clue. It makes me wonder what they were trying to accomplish when they invented this molecule. Does anyone know that?>>
modafinil is a derivative of adrafinil. adrafinil, apparently, is from a series of alpha-1 agonists. The early theories all center on alpha-1 agonism as the mechanism of action, since the actions of both molecules are blocked by prazosin.
Its original use, which remains its major indication, was for narcolepsy.
But from what I have read, investigators were caught off guard by the molecules' properties, e.g.:
Eur J Pharmacol. 1990 May 3;180(1):49-58.
Central alpha 1-adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals.Duteil J, Rambert FA, Pessonnier J, Hermant JF, Gombert R, Assous E.
Centre de Recherches du Laboratoire L. Lafon, Maisons-Alfort, France.
Single administration of the new drug modafinil was followed by an increase in locomotor activity in mice and in nocturnal activity in monkeys. Stereotyped behaviour in mice and rats, and potentiation of amphetamine-induced stereotyped behaviour were not observed; however, at the highest dose used, a slight potentiation of apomorphine-induced stereotyped behaviour was observed in rats. The modafinil-induced increase in locomotor activity in mice was prevented by the centrally acting alpha 1-adrenoceptor antagonists, prazosin and phenoxybenzamine, and by reserpine but not by the mixed dopamine D-1/D-2 antagonist, haloperidol, the dopamine D-2 antagonist, sulpiride, the peripherally acting alpha 1-adrenoceptor antagonist, phentolamine, the alpha 2-adrenoceptor antagonist, yohimbine, the beta-adrenoceptor antagonist, propranolol, or by the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine. Likewise, the modafinil-induced increase in nocturnal activity in monkeys was prevented by prazosin. Interestingly, modafinil did not produce obvious peripheral sympathetic effects in mice and rats (no salivation, no contraction of the pilomotor muscles, slight mydriasis only at high doses). Therefore, modafinil appears to produce a strong stimulating effect in rodents and in primates. These effects could be linked to modulation (stimulation) of central alpha 1-adrenoceptors unaccompanied by peripheral sympathetic effects, which is unexpected.
I wish I were less ADHD-afflicted and could get past the second chapter of my organic chem book, which has been buried beneath books on modal logic and grammatical theory, so I could see what its chemical structure 'looks' like. right now, I can't even tell you what my organic chem book looks like.
oh yes, the drug also attracted the interest of the French military. Modafinil was used by French soldiers during the First Gulf War to improve performance during sleep deprivation.-z
poster:zeugma
thread:612884
URL: http://www.dr-bob.org/babble/20060227/msgs/613859.html