General
The Future Synthetic Drugs Of Abuse
Designer Drugs - part 3 of 3
By Donald A. Cooper
From The DEA
Stimulants
Relative to medical usage, a stimulant is defined to be an agent that arouses organic activity, strengthens the action of the heart, increases vitality, and promotes a sense of well being.
However, as per the medical definition, the effects produced by a stimulant may not be a very accurate term for the effects sought by those who abuse these compounds.
For instance, at dose levels usually equated with heavy abuse, both amphetamine (Hampton 1961; Angrist et al. 1969) and methamphetamine (Liddel and Weil-Malherbe 1953) are thought to be psychotogenic.
Therefore, several of the amphetamines could be discussed as hallucinogens; however, it seems most likely that a substantial portion of the abuse of stimulant drugs is performed with the intention of inducing a state of euphoria (Brown 1972).
Historically, the abuse of stimulants (euphoriants) has been largely confined to amphetamine, derivatives thereof, and cocaine.
Some of the amphetamine derivatives which have been controlled under U. S. law are methamphetamine, N-ethylamphetamine, fenethylline, phenmetrazine (preludin), phendimetrazine, benzphetamine, chlorphentermine, clortermine, diethylpropion, methylphenidate, pemoline, and amphetamine.
Other derivatives of amphetamine which have been encountered in samples submitted to DEA laboratories, but have not yet been brought under legal controls, are bis-methamphetamine, fencamfamine (Nied and Smith 1982), N,N-dimethylamphetamine (dimephenopan) (Allen, A. personal communication), and an analog of pemoline, 4-methylaminorex (U4EUH) (Inaba and Brewer 1987).
Since pemoline is listed under Schedule IV of the CFR and 4-methylaminorex is clearly an analog Of pemoline, it falls outside of the guide-lines set forth in the CsA amendment; therefore, 4-methylaminorex is not controlled under U. S. law.
It is equally clear that bis-methamphetamine and N,N-dimethylamphetamine do fall under the CsA guidelines and would be considered controlled substances under tile CsA amendment.
However, it may be that N,N-dimethyl-amphetamine may not enjoy a long history in the clandestine market as at least one work states that it is considerably less potent than methamphetamine (Schaeffer et al. 1975).
Most of the adrenomimetic activity-structure relationships were delineated in the previous discussion on psychotomimetic phenylethylamines.
The principle difference between the pharmacological action, as related to structure for these two classes of compounds, is determined by the nature of the substituents on the aryl system.
In general it is noted that substituents on the aryl system which are ortho-para directors tend to produce psychotogenic compounds with methoxy substituents often producing the most pharmacologicaly active hallucinogens.
However, there are several exceptions to this general statement, not the least of which is exemplified by substitution on the phenyl ring of the electrophilic hydroxy moiety which in nearly every case either eliminates or greatly reduces hallucinogenic activity.
On the other hand, adrenomimetic activity is clearly enhanced by branching of phenylethylamine at the carbon alpha to the amine nitrogen and is maintained at reasonable levels by substitution to the nitrogen as shown in table II. Both N-ethylamphetamine and N,N-dimethylamphetamine have appeared in the illicit market and clearly follow the points made above.
However, a market factor has been introduced by the fact that phenyl-2-propanone (P2P) has been listed under the CFR as a Schedule II substance.
Hence, it makes little sense for the clandestine chemist to produce CsA's of phenylethylamines which have potencies that are less than methamphetamine if he is going to produce his CsA's in a synthesis that uses P2P.
The recent illicit use of 4-methylaminorex may well be the result of the clandestine chemist trying to circumvent the legal problems associated with P2P.
On the other hand, the sum total of methamphetamine still being covertly produced suggests that the control of P2P has not appreciably reduced the drug's availability in the illicit marketplace.
As before, if the chemist is not concerned about the CsA amendment, the structural possibilities offered by Table II, less the three controlled substances that are included, provides for thirteen possible future stimulant CsA's.
It would seem that the single most logical next stimulant CsA would be N-methyl-[alpha]-ethylphenylethylamine.
This compound should be pharmacologicaly very similar to methamphetamine and synthesis could employ 1-phenyl-2-butanone instead of P2P.
Alternatively, the use of 1-(4-fluorophenyl)propan-2-one, in place of P2P, would almost certainly give a product with adrenomimetic properties, and may in fact be considerably more potent than methamphetamine.
The clandestine chemist of limited chemical sophistication may not notice the structural similarity of such compounds as methylphenidate, phenmetrazine, 4-methylaminorex, and amphetamine.
If he does recognize the constancy of the phenylisopropylamine substructure in these compounds he may well explore the literature in an effort to determine the structural outer limits for the phenylisopropylamine stimulants.
At what may be near these structural outer limits he will find a class of compounds which are correctly referred to as conformationally rigid phenylethylamines.
Some of the conformationally rigid phenylethylamines are fencamfamine, tranylcypromine (2-phenylcyclopropylamine), 2-phenyl-cyclohexylamine (Smissman and Pazdernik 1973), 2-amino-3- phenyl-trans-decalin, and 2-aminotetralin (Barfknecht et al. 1973).
The potency of most of these compounds is highly dependent upon stereochemistry. Those isomeric forms which most closely approximate the anti periplanar conformation observed for amphetamine in solution are the most potent stimulants.
Hence, transtranylcypromine is considerably more potent than is the cis isomer (Grunewald et al. 1976). The most active isomer of these compounds does not approach the potency of the simple phenylisopropylamines.
Given this reduction in potency for the most active isomers one would think that, in order to obtain amiable product for the illicit market, a stereo specific synthesis would be required.
This feature, along with a lowered potency for even the more active isomers, may very well exclude the conformationally rigid phenylethylamines from the synthetic repertoire of the surreptitious chemist.
Hence, it is a reasonable expectation that those conformationally rigid phenylethylamines which will be abused in the future will be obtained by diversion of limit supplies rather than by clandestine syntheses.
Unfortunately, it seems to be an axiom that any compound which has any possibility of altering man's perception of himself or his surroundings will at some time be abused.
Propylhexadrine, although not an extreme example, is nevertheless an example of a compound which has been abused although adrenogenic potency is far less than that of methamphetamine (Garriott 1975).
Therefore, one must expect some abuse of the conformationally rigid phenylethylamines to occur. It would be my guess however, that the extent of such abuse will never be large.
The parent structure for 4-methylaminorex has been known since 1889 (Gabriel 1889) and many derivatives thereof have been studied for pharmacological activity.
Pemoline (2-amino-5-phenyl-2-oxazolin-4-one) (Traube and Ascher 1913; Howell et al. 192) is presently a controlled substance in the U. S., is classified as a stimulant, and is listed under Schedule IV of the CFR. Poos (personal communication) synthesized and performed pharmacological studies for some twenty seven 2-amino-2-oxazoline isomers of which aminorex and 4-methylaminorex were two.
In this work, aminorex and 4-methylaminorex, regardless of the steroisomer employed, were found to have anorectic activity on par with d-amphetamine.
However, adrenomimetic activity of 4-methylaminorex was determined to be less than that of amphetamine and similar to phenmetrazine (Patil and Yamauchi 1970).
It has been suggested that the effectiveness of stimulant drugs as appetite suppressants are the result of the fact that the user forgets to eat and that this behavior is in direct proportion to the adrenomimetic activity of the drug (Cutting 1969).
Contrary to previously cited work this suggests that aminorex may in fact be as potent an adrenomimetic as amphetamine. In any case, Poos (personal communication) highlighted eight compounds which may have adrenomimetic activity similar to those of amphetamine and methamphetamine.
Shown below and listed in decreasing order of anoretic activity they are:
1) 2-amino-5-(4-fluorophenyl)-2-oxazoline
2) 2-amino-5-(4-Chlorophenyl)-2-oxazoline
3) 2-amino-5-(3-trifluoromethylphenyl)-2-oxazoline
4) 2-amino-5-(4-bromophenyl)-2-oxazoline
5) 2-amino-5-phenyl)-2-oxazoline [aminorex]
6) 2-amino-5-(4-trifluoromethylphenyl)-2-oxazoline
7) 2-dimethylamino-4-methyl)-5-phenyl-2-oxazoline
8) 2-amino-4-methyl-5-phenyl-2-oxazoline [4-methylaminorex].
Although not mentioned in this work, one would immediately assume that the 4-fluoro- and 4-chloro-phenyl derivatives of compounds 7 and 8 would also have significant anoretic activity.
Given the astoundingly simple synthetic process required to produce these compounds, and the fact that the 4-halogen substituted aryl derivatives would require precursors unlikely to titillate the interest of law enforcement agencies, these compounds will most probably be made in future clandestine syntheses.
It is also conceivable that some enterprising clandestine chemist will wonder if appropriately substituted methoxy derivatives will have psychotomimetic properties.
The literature contain many references to stimulant drugs of variant structures which may not spark the interest of the less knowledgeable clandestine chemist.
However, nearly all of these compounds can be accessed through literature searches for either derivatives of phenylethlamines or stimulant compounds.
Several compounds which serve as examples are fenmetramid (Ippen 1968), prolintane, 1-([alpha]-propylphenylethyl) pyrrolidine (Heinzelman et al. 1960; Hollister and Gillespie 1970), pyrovalerone (1-(4-methylphenyl)-1-oxo-2-pyrrolidino-n-pentane) (Heinemann and Vetter 1965; Heinemann and Lukacs 1965), N,3,3-trimethyl-1-(m-tolyl)-1-phthalanpropylamine (Gill et al. 1970), zylofuramine ([alpha]-benzyl-n-ethyltetrahydro-D-threo-furfurylamine)(Harris et al. 1963), a series of N-substituted phentermine compounds (Borella et al. 1970), 4-hydroxyamphetamine (Mannich and Jacobsohn 1910; Hoover and Hass 1947a,b), N-methylephedrine (Smith 1927), nylidrin, N-(1-methyl-3-phenylpropyl)-2-hydroxy-2-(4-hydroxy-phenyl-l-methyl-ethylamine (Treptow et al. 1963), pheniprazine, [alpha]-methyl-phenylethyl hydrazine (Zbinden et al. 1960), and N,N-diethyl-2-phenylcyclopropylamine (SKF). All of these compounds are derivatives of phenylethylamine with the exception of N,3,3-trimethyl-1-(m-tolyl)-1-phthalanpropylamine which is a 3-phenyl-3-propylamine substituted onto a phthalane at C-1.
A number of closely allied derivatives of this compound have been examined and are classified as weak stimulants.
Fenmetramide is noteworthy in that it is a 2-one derivative of phenmetrazine. Any and all of these compounds are subject to abuse; however, the synthesis of simple phenylethylamine derivatives would not appear to offer the clandestine chemist any advantage over the synthesis of methamphetamine.
The reasons for this statement are that pharmacological studies have not identified other phenylethylamine structures with stimulant activity appreciably greater than methamphetamine and that either P2P or the [beta]-hydroxyphenylisopropylamines are the preferred precursors. However, in any case, the U. S. CsA amendment should apply for all compounds containing the phenylethylamine substructure.
The stimulant drugs phenmetrazine (preludin) and methylphenidate (ritalin) are controlled under Schedule II of the CFR.
These compounds rank approximately half-way between caffeine and amphetamine in potency (Meier et al. 1954; Tripod et al. 1954a; Gruber et al. 1956).
The published synthesis of phenmetrazine, which would seem to be most amenable to the clandestine laboratory, is given in the work by Otto (Otto 1956).
The reaction involves the acid-catalyzed cyclization of N-hydroxyethylnorephedrine (N-hydroxyethylphenylpropanolamine). However, this reaction places severe limits on the production of CsA's because suitable precursors are limited.
For instance, phenmetrazine CsA could be prepared from compounds such as N-ethyl-2,2-hydroxyphenyl-1-methylethylamine, 1,1-hydroxyphenyl-2-aminobutane, etc, but limited commercial availability would generally require synthesis of these compounds.
Additionally, the product CsA would clearly be perceived, even by the untrained, as being structurally similar to phenmetrazine and thereby would be a controlled substance under the CsA amendment.
Further, the corresponding phenylethylamine which could be made from these precursors, although also under the purview of the CsA amendment, would most probably have greater adrenergic activity than the phenmetrazine derivative. Hence, clandestine production of phenmetrazine CsA's would most likely be an uncommon event.
Pipradrol is a controlled substance under CFR Schedule IV and can be considered to be an analog derivative of methylphenidate. Methylphenidate can be synthesized by the method of Hartmann and Panizzon (1950).
The product exists as two diastereoisomeric enantiomer pairs, one of which is the active stimulant, threo-dl-methylphenidate (Weisz and Dudas 1960), while the other is inactive as a stimulant.
Threo-methylphenidate accounts for only 20% of the final reaction product (Rometsch 1958;1960). The synthesis of pipradrol may be more amenable to the clandestine laboratory as it is a relatively simple synthesis and isolation of the final product is straightforward.
An appropriate C-2 substituted, N-protected piperidine is a suitable precursor for what is essentially a two step synthesis (Tilford et al. 1948; Werner and Tilford 1953).
Numerous derivatives of methylphenidate and pipradrol have been synthesized with the result that structure activity relationships have been well defined (Scholz and Panizzon 1954; Tilford and Van Campen 1954; Heer et al. 1955; Fabing 1955; McCarty et al. 1957; Sheppard et al. 1960; Belleau 1960; Winthrop and Humber 1961; Portoghese and Malspeis 1961; Wilimowski 1962; Lachman and Malspeis 1962).
There is little incentive, beyond the not inconsiderable pressure of an already existing and ready market, for producing clandestine CsA's of methylphenidate.
However, there are a number of pipradrol derivatives described in the last cited references which are suitable for clandestine production.
A best bet for a future CsA is the most potent adrenomimetic compound in this series, 2-diphenyl-methylpiperidine (Tripod et al. 1954b), which is estimated to be as potent as methamphetamine (Sury and Hoffmann 1954).
In a very similar article to this paper, Drugs of Abuse in the Future, Shulgin (1975) suggested that levophacetoperane could well be a future clandestine CsA.
However, this compound shares the same limitations for clandestine synthesis as does methylphenidate, in that only one diastereoisomer is active (Jacob and Joseph 1960) and it is less potent than methylphenidate (Dobkin 1960).
Although the phenylisopropylamine substructure is an integral part of most known stimulants, the well known and much abused stimulant, cocaine, does not share this structural feature.
The cocaine molecule instead compares more closely to the structure of acetylcholine. The synthesis of cocaine has recently been revisited by Casale and many of the procedural techniques are explained in sufficient detail so that any competent organic chemist can now make the C-3 equatorial cocaines (Casale 1987); however, it is still a tedious and demanding synthesis, and in my opinion will only be encountered on rare occasions in clandestine laboratories.
The particular pharmacological behavior of cocaine is unquestionably due in major part to the stereochemistry of the molecule as determined by the fused bicyclic tropane ring system (Clarke et a/. 1973).
Given the present difficulties associated with the synthesis of the tropanes and the ready availability of the natural product, it is unlikely that a synthetic CsA of this compound will appear in the near future.
However, it is the case that certain modifications of natural cocaine can result in products having substantially greater potencies than cocaine.
The compounds 2-carbomethoxy-3-(4-fluorophenyl)tropane and 2-carbomethoxy-3-phenylnortropane are both some 60 times more potent than cocaine (Clarke et al. 1973).
These compounds could well be of interest to some clandestine chemists as taking one kilogram or cocaine and converting it into a product some sixty times more potent would obviously be quite cost effective.
In Drugs of Abuse in the Future, Shulgin (1975) directed attention to another stimulant which also does not contain the phenylethylamine substructure and, in fact, is reminiscent of the depressant glutethimide.
The compound is known commercially as bemegride, 4-ethyl-4-methylpiperidine-2,6-dione, and was first synthesized by Thole and Thorpe in 1911 (Thole and Thorpe 1911).
The principal medical use is as an analeptic in barbiturate poisoning. As a stimulant, bemegride is approximately equal to phendimetrazine and pemoline in potency.
Although glutethimide and bemegride are structurally similar, their pharmacokinetics are diametrically opposed. Hence, bemegride cannot be described as a CsA.
Bemegride, by virtue of being a stimulant, has an obvious potential for abuse, although under the conditions of abuse, rather large quantities of the drug will be required.
Increasing the possibility of bemegride abuse are the facts that the synthesis of the compound is not difficult and, of course, does not use either a controlled or watched substance as a precursor (Benica and Wilson 1950).
Analgesics
Literature covering the analgesics is so voluminous that a review of the published data on the subject is far beyond the scope of this work.
Most of the potent analgesics are modeled after features found within the structure of morphine and some literature detailing these structural features has been published by Paul Janssen (Janssen 1960; 1961; 1962a,b; 1968).
Despite a significant passage of time, the structure activity relationships established in these works still comprise a very sizable portion of our empirical knowledge on this subject.
Some 13 years ago, Shulgin (1975) provided a short overview of many of the known major classes of analgesics. The following constitutes a similar listing:
1. morphines
2. morphinans and isomorphinans
3. benzomorphans
4. pethidines (meperidines), prodines, and ketobemidones
5. fentanyls
6. 3,3-diphenylpropylamines (methadone, propoxyphene)
7. thiambutenes
8. phenampromide and l-dialkylaminoethyl-2-(4-alkyloxy)benzyl-5-nitrobenzimidazols
9. pirinitramide derivatives
Numerous works have dealt with the syntheses and pharmacological testing of derivatives of the structures listed above.
Synthetic procedures have been improved and refinements aimed at the tailoring of specific analgesics to fulfill certain medical needs have been addressed.
However, it has been since 1975 that no work has been found introducing a new class of analgesics of either unusual potency or particularly well suited to synthesis in clandestine laboratories.
There has been discovered one compound which may be of minor interest in that it is an analgesic with potency similar to morphine and can be described as a ring condensation product of N,N',3-trimethyl-5-hydroxytryptamine (Brossi 1985).
In any discussion of synthetic analgesics one must include the so called Bentley compounds. These compounds are not, in the purest sense, synthetic analgesics as they are C-ring etheno Diels Alder adducts of thebaine (Bentley et al. 1967a).
Etorphine is perhaps the best known compound in the series and has analgesic activity approximately 1000 times that of morphine (Bentley et al. 1967b; Hutchins et al. 1981).
Although reaction conditions appear to be critical, the synthesis of etorphine derivatives involves what is essentially a two step reaction with methylvinylketone and an appropriate organometallic reagent (Haddlesey et al. 1972; Hoogsteen and Hirshfield 1983).
Hence, the only expected difficulty in the clandestine synthesis of these compounds would lie in the initial acquisition of the thebaine.
Therefore, it is somewhat surprising that either etorphine or derivatives thereof have not become a contributor to illicit analgesic supplies.
On the other hand, if etorphine were to be admixed with some less potent analgesic, such as heroin, it is doubtful that it would ever be detected. In his 1975 article, Shulgin pointed to meperidine, prodine, and ketobemidone as possible models for Drugs of Abuse in the Future.
There are some who think that Shulgin's comments were somewhat of a self fulfilling prophecy as it is felt that his article is well worn within the circles of clandestine laboratory operators (Sapienza, F. personal communication).
Supporting this premise, at least to some extent, is the fact that the appearance of the first known fentanyl, China While, did not occur until 1979 (Henderson, G. 1.. personal communication).
However, it is also the case that desmethylprodine (MPPP) was first encountered in a DEA laboratory sample submission in July of 1973 (Kram, T. personal communication), a full two years before Shulgin published his article.
The probability that CsA's of prodine will constitute any appreciable quantity of the clandestine analgesic market in the future is relatively remote.
The well publicized neuro-toxicity of the prodine dehydration product, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (Langston et at. 1983; Markey et al. 1985; Fries et al. 1986; Parkes 1986), coupled with a limited scope of derivatives having appreciable analgesic activity (Berger et al. 1947; Ziering and Lee 1947; Beckett et al. 1957; Loew and Jester 1975) would seem to remove prodine from consideration as a model for CsA's.
The fact that the 3-allyl analog of MPTP is not thought to be neurotoxic (Brossi 1985) and the corresponding prodine analog has greater analgesic activity than does betaprodine (Ziering et al. 1957) may be of some interest to the clandestine laboratory operator. However, allylprodine is already controlled under Schedule 1.
A prodine derivative which may be found in a future clandestine laboratory is [alpha]-promedol, (Fries and Portoghese 1976).
Analgesic activity for the unresolved stereoisomers of promedol is approximately ten times that of morphine, but there is some increased difficulty associated with the synthesis and neurotoxicity for it's MPTP analog is a real possibility.
It is also the case that [alpha]-promedol is listed in CFR Schedule I under the name of trimeperidine.
In any event, the syntheses of prodine CsA's arc fraught with considerable risk from the inadvertent production of either MPTP or an as yet unexplored congener also having neurotoxic properties.
It is worth noting that at one time MPTP was tested for use as an insecticide and that there are reports of workers handling MPTP who have suffered full blown Parkinsonian symptoms (Shafer, J. personal communication).
Meperidine (pethidine, demerol) is approximately 50% as potent an analgesic as is morphine and has a safety margin of only 4.8 as compared to 71 for morphine (Janssen 1985).
Hence, one would assume that the continued abuse of meperidine is most probably related to the east with which it can be diverted from commercial channels rather than it's applicability to drug abuse per se.
It has been noted that there are some 4000 compounds which may be related chemically to meperidine (Burger 1970).
It should be pointed out that of these 4000 compounds, many are not classified as analgesics, and they must also include the closely allied prodine and ketobemidone derivatives.
The most potent analgesics of the meperidine class of compounds, as is the case with the prodine class of compounds, all appear to already be controlled under Schedule I and the less potent but clinically useful derivatives controlled under Schedule II.
The most interesting compound from the view point of clandestine synthesis would have to be phenoperidine, as analgesic activity is approximately 30 times that of morphine and the safety margin is increased, relative to meperidine, quite substantially (Janssen 1985).
Fentanyl is an analgesic of high potency, approximately 300 times that of morphine, which was developed by Janssen in 1962 (Janssen 1962b) and is N-[(2-phenylethyl)-4-piperidyl]-N-phenyl-propanamide.
The first CsA of fentanyl came to the attention of law enforcement in late 1979 but was not identified until 1981 (Allen et al. 1981). In the next three years a procession of new fentanyl CsA's appeared in the illicit drug market.
The abuse of fentanyl CsA's peaked in 1985 and has since decreased dramatically (Henderson 1987), a phenomena which was the result of DEA successfully terminating the operation of the responsible laboratories.
However, the ripple effect is still being felt as international and national meetings have been held to discuss the problems presented by CsA's.
Also, legislation, such as the U. S. CsA amendment, has been passed in order to allow law enforcement to deal more efficiently with the analog problem.
It is the author's opinion that fentanyl CsA's will be back as the future analgesic drugs of abuse.
The thoughts behind this statement are that the published synthesis schemes for the fentanyl compounds allow for the use of wide variety of precursors as discovered by the confiscated notes from an anonymous clandestine laboratory that synthesized a drug, based on information presented in two separate volumes of the Journal of Organic Chemistry (Anon. 1957; Janssen 1962a; Riley et al. 1973; Van Bever et al. 1974, Van Daele et al. 1976). Also, several fentanyl derivatives have such high potencies that the quantities required to be synthesized are trivial.
For instance, carfentanil is approximately 4000 times as potent as heroin and has an extremely favorable therapeutic index (Janssen 1985).
Hence, an easy week's work for two chemists could provide 1 (one) kilogram of carfentanil which would be equivalent to 40 metric tons of pure heroin.
In the course of this article, several points have been made concerning those forces which will control the appearance of future synthetic drugs of abuse.
The most important of these factors is user acceptance of the marketed drug. Needless to say, the typical clandestine drug dealer and/or chemist is not overly concerned with the health of the user.
However, they are concerned with having a ready market for their product. A reputation for selling bad stuff would not be conducive to good business. A recent example of this can be found in MPPP.
The second most important market controlling factor is law enforcement control of the industry. A recent example would be the effects produced when P2P was placed under legal controls.
The response so far has been two fold; first there has been a concerted move to either more fundamental precursors or to synthetic routes utilizing [beta]-hydroxyphenylethylamines, and second, there has been an apparent increase in the abuse of 4-methylaminorex.
Hence, the methamphetamine market is in a state of flux as a direct result of law enforcement activity and either a CsA will be found which will provide both the user and the clandestine drug chemist with the same advantages as methamphetamine or a new precursor synthesis scheme will be found which will offer nearly the same advantages as P2P.
It is axiomatic that for drugs of moderate potency arid high consumer demand, such as methamphetamine, a synthesis scheme must be relatively straightforward as it must be amenable to the limited expertise available in the clandestine laboratories in order to meet consumer demand.
In this work, only an occasional attempt was made to address the difficulties associated with the practical synthesis of the various derivatives discussed. Some of the compounds discussed do not have conveniently configured precursors that are commercially available.
Hence, synthesis of some of these compounds require using the precursors earth, fire, and water. Additionally, as the number and complexity of substitution on any given chemical structure increases, there is a corresponding increase in the number of byproducts and a decrease in the ultimate yield of target compound.
In total then, some of the compounds mentioned in this work are not practical, especially considering the clandestine laboratory, given the present state of synthetic knowledge.
However, as time moves on, more efficient and direct methods of synthesis will be found and made available to the informed reader through the scientific literature.
This point is easily exemplified even by the work of our own forensic scientists (Sy and By 1984; Casale 1987). The clandestine chemist of the future will be more sophisticated than those of the present and compounds not yet conceived of will be within their reach.
Consumer preferences and law enforcement activities are the two dominate forces affecting today's illicit drug markets.
While staying within the confines of consumer demand, the clandestine chemist of the future will synthesize those drugs having the highest possible potency in an effort to limit his exposure to law enforcement activities and to expand his illicit business as well.
Acknowledgement: The author wishes to express his appreciation for the invaluable assistance of Dr. Robert Klein, Ann Wimmers, and Charles Harper in the preparation of this article.
Definitions
Analgesic 1) causing analgesia or freedom from pain. 2) a pain relieving remedy.
Analog Compound with similar electronic structure but different atoms. Controlled Substances Those drug substances which are listed as of January 1, 1988 under schedules I through V of the United States Title 21 Code of Federal Regulations (CFR) section 1300 to end.
Derivative An organic compound containing a structural radical similar to that from which it is derived, for example, benzene derivatives containing the benzene ring.
Homolog Member of a series of compounds whose structure differs regularly by some radical, for example, methylene, from that of its adjacent neighbors in the series.
Schedule I Schedule I is a listing of those substances which are controlled under U. S. federal laws, are deemed to have a high potential for abuse, and for which there is no accepted medical use.
Schedule II Schedule II is a listing of those substances which are controlled under U. S. federal laws, are deemed to have a high potential for abuse, and for which there is a accepted medical use.
page 1 page 2 page 3
Books Drug Identification:
Designer and Club Drugs Quick Reference Guide
The author worked as an undercover detective in rave clubs for several years. This is a condensed version of what he learned that will be of use to parents, authorities, and users alike.
It lists symptoms people look for when judging if someone is using, paraphernalia used for different designer drugs, as well it provides pictures of what various designer drugs looks like.
Drug Identification Synthetic Panics:
The Symbolic Politics of Designer Drugs
Just as every new drug creates a panic that is fueled by the media, this book looks at the panic over designer drugs created by those interested in making money off of lies and deception.
Accurate and non biased, this is worth getting for anyone who wants to know the truth. Includes chapters on; Speed Kills, The PCP Crisis, Suppressing Ecstasy, The CAT Attack, Redneck Cocaine, Methamphetamine, Rave Drugs and Rape Drugs, and much more.
Synthetic Panics
More Designer Drug Books Designer Drug books from Amazon
Designer Drug Related More Designer Drug Articles