View source for Dimethylheptylpyran

{{Drugbox|
|IUPAC_name = 6,6,9-trimethyl-3-(3-methyloctan-2-yl)-
7,8,9,10-tetrahydrobenzo[c]chromen-1-ol
| image = Dimethylheptylpyran.svg
| width = 220
| CAS_number= 32904-22-6
| ATC_prefix= none
| ATC_suffix=
| PubChem= 36276
| DrugBank=
| C=25 | H=38 | O=2
| molecular_weight = 370.57 g/mol
| bioavailability=
| metabolism = 
| elimination_half-life= 20-39 hours
| excretion = 
| pregnancy_category =
| legal_status = Schedule I / Class A
| routes_of_administration= 
}}

'''Dimethylheptylpyran''' ('''1,2-dimethylheptyl-Δ<sup>3</sup>THC''', '''DMHP''', '''A-40824''', '''EA-1476''') is a synthetic analogue of [[tetrahydrocannabinol|THC]], which was invented in&nbsp;1949 during attempts to elucidate the structure of Δ<sup>9</sup>-THC, the active component of [[cannabis]].<ref>Adams R, Harfenist M, Loewe S. New Analogs of Tetrahydrocannabinol. XIX. ''Journal of the American Chemical Society''. 1949; 71(5):1624-1628.</ref> DMHP is a pale yellow, viscous oil which is insoluble in water, but dissolves in alcohol or non-polar solvents.

==Effects==
DMHP is similar in structure to THC, differing only in the position of one double bond, and the replacement of the 3-pentyl chain with a 3-(1,2-dimethylheptyl) chain.<ref>Razdan RK. The Total Synthesis of Cannabinoids. Wiley-Interscience 1980.</ref> It produces similar activity to THC, such as [[sedative]] effects, but is considerably more potent,<ref>Wilkison DM, Pontzer N, Hosko MJ. "Slowing of cortical somatosensory evoked activity by delta 9-tetrahydrocannabinol and dimethylheptylpyran in alpha-chloralose-anesthetized cats." ''Neuropharmacology''. 1982 Jul;21(7):705-9. PMID 6289158</ref> especially having much stronger [[analgesic]] and [[anticonvulsant]] effects than THC, although comparatively weaker psychological effects. It is thought to act as a [[Cannabinoid receptor|CB<sub>1</sub>]]&nbsp;[[agonist]], in a similar manner to other similar [[cannabinoid]] derivatives.<ref>Parker LA, Mechoulam R. "Cannabinoid agonists and antagonists modulate lithium-induced conditioned gaping in rats." ''Integrative Physiological and Behavioural Science''. 2003 Apr-Jun;38(2):133-45. PMID 14527182</ref>

==Investigation as non-lethal incapacitating agent==
DMHP and its O-[[acetate]] [[ester]] were extensively investigated by the [[United States and weapons of mass destruction#Chemical weapons|US military chemical weapons program]] in the [[Edgewood Arsenal experiments]], as possible non-lethal incapacitating agents.<ref>[http://books.nap.edu/openbook.php?record_id=9136&page=79 Possible Long-Term Health Effects of Short-Term Exposure To Chemical Agents, Volume 2: Cholinesterase Reactivators, Psychochemicals and Irritants and Vesicants (1984) Commission on Life Sciences. The National Academies Press. pp79-99.]</ref> 

DMHP has three [[stereocenter]]s and consequently has eight possible [[stereoisomer]]s, which differ considerably in potency. The [[racemic]] mix of all eight isomers of the O-acetyl ester was given the code number EA-2233, with the eight individual isomers numbered EA-2233-1 through EA-2233-8. The most potent isomer was EA-2233-2, with an active dose range in humans of 0.5-2.8&nbsp;μg/kg (i.e. ~35-200&nbsp;μg for a 70&nbsp;kg adult). Active doses varied markedly between individuals, but when the dose of EA-2233 was taken up to 1-2&nbsp;mg, all volunteers were considered to be incapable of performing military duties, with the effects lasting as long as 2-3&nbsp;days. 

DMHP is metabolised in a similar manner to THC, producing the active metabolite 11-hydroxy-DMHP, but the [[lipophilicity]] of DMHP is even higher than that of THC itself, giving it a long duration of action and an extended half-life in the body of between 20-39&nbsp;hours, with the half life of the 11-hydroxy-DMHP metabolite being longer than 48&nbsp;hours.

Cannabinoids as a class are generally safe compounds with a large safety margin, making potent cannabinoid drugs ideal as potential non-lethal incapacitating agents. DMHP and its esters produce [[sedation]] and mild [[hallucinogenic]] effects similar to large doses of [[Tetrahydrocannabinol|THC]], but in addition to this they also cause pronounced [[hypotension]] (low blood pressure) which occurs at doses well below the hallucinogenic dose, and can lead to severe [[dizziness]], [[fainting]], [[ataxia]] and [[muscle weakness]], sufficient to make it difficult to stand upright or carry out any kind of vigorous physical activity. The acute toxicity of DMHP was found to be low in both human and animal studies, with the [[Therapeutic index|ratio of ED<sub>50</sub> to LD<sub>50</sub>]] in animals being around 2000x, with death ultimately resulting from a combination of hypotension and [[hypothermia]] and preventable with supportive treatment.

The combination of strong incapacitating effects and a favourable safety margin led the Edgewood Arsenal team to conclude that DMHP and its derivatives, especially the O-acetyl ester of the most active isomer, EA-2233-2, were among the more promising non-lethal incapacitating agents to come out of their research program. However they were disadvantaged by producing severe hypotension at incapacitating doses, and were not as effective as the more widely publicised anticholinergic agents such as [[3-Quinuclidinyl benzilate]] which had also already been weaponised.<ref>James S. Ketchum. Chemical Warfare Secrets Almost Forgotton. ChemBooks Inc. 2006. ISBN 978-1-4243-0080-8</ref> Funding for continued development was ultimately not approved, and the cannabinoid research program was indefinitely suspended along with the rest of the Edgewood Arsenal experiments in the late 1970s, in accordance with the US commitment to cease research into chemical weapons under disarmament treaties.

{{cannabinoid-stub}}

== References ==
<references />

{{cannabinoids}}
{{Chemical warfare}}

[[Category:Cannabinoids]]
[[Category:Benzochromenes]]
[[Category:Phenols]]
[[Category:Incapacitating agents]]
[[Category:2Fix]]