Valnoctamide
Encyclopedia
Valnoctamide has been used in France as a sedative
-hypnotic
since 1964. It is a structural isomer of valpromide
, a valproic acid
prodrug
; unlike valpromide, however, valnoctamide is not transformed into its homologous acid
, valnoctic acid, in vivo
.
since 1969 and was still being investigated in 2000 and 2003.
It was studied for neuropathic pain
in 2005 by Winkler et al., with good results: it had minimal effects on motor coordination
and alertness at effective doses, and appeared to be equally effective as gabapentin
.
RH Belmaker, Yuly Bersudsky and Alex Mishory started a clinical trial of valnoctamide for prophylaxis of mania
in lieu of the much more teratogenic valproic acid or its salts.
s of valnoctamide are mostly minor and include somnolence
and the slight motor impairments mentioned above.
hydrolase
the serum levels of carbamazepine-10,11-epoxide, the active metabolite
of carbamazepine
, sometimes to toxic levels.
compound with four stereoisomers, all of which were shown to be more effective than valproic acid in animal models of epilepsy and one of which [(2S,3S]-valnoctamide) was considered to be a good candidate by
Isoherranen, et al. for an anticonvulsant in August 2003.
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
-hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
since 1964. It is a structural isomer of valpromide
Valpromide
Valpromide is a carboxamide derivative of valproic acid used in the treatment of epilepsy and some affective disorders. It is rapidly metabolised to valproic acid but has anticonvulsant properties itself...
, a valproic acid
Valproic acid
Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...
prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
; unlike valpromide, however, valnoctamide is not transformed into its homologous acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
, valnoctic acid, in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
.
Indications
In addition to being a sedative, valnoctamide has been investigated for use in epilepsyEpilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
since 1969 and was still being investigated in 2000 and 2003.
It was studied for neuropathic pain
Neuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
in 2005 by Winkler et al., with good results: it had minimal effects on motor coordination
Motor coordination
thumb|right|Motor coordination is shown in this animated sequence by [[Eadweard Muybridge]] of himself throwing a diskMotor coordination is the combination of body movements created with the kinematic and kinetic parameters that result in intended actions. Such movements usually smoothly and...
and alertness at effective doses, and appeared to be equally effective as gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...
.
RH Belmaker, Yuly Bersudsky and Alex Mishory started a clinical trial of valnoctamide for prophylaxis of mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
in lieu of the much more teratogenic valproic acid or its salts.
Side effects
The side effectAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s of valnoctamide are mostly minor and include somnolence
Somnolence
Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
and the slight motor impairments mentioned above.
Interactions
Valnoctamide is known to increase through inhibition of epoxideEpoxide
An epoxide is a cyclic ether with three ring atoms. This ring approximately defines an equilateral triangle, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in...
hydrolase
Hydrolase
In biochemistry, a hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. For example, an enzyme that catalyzed the following reaction is a hydrolase:-Nomenclature:...
the serum levels of carbamazepine-10,11-epoxide, the active metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, sometimes to toxic levels.
Chemistry
Valnoctamide is a racemicRacemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
compound with four stereoisomers, all of which were shown to be more effective than valproic acid in animal models of epilepsy and one of which [(2S,3S]-valnoctamide) was considered to be a good candidate by
Isoherranen, et al. for an anticonvulsant in August 2003.